Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

New Synthesis of Perhydrotriazolotriazoles Catalyzed by TiCl4 under Ambient Conditions

  • Safari, J. (Laboratory of Organic Compound Research, Department of Organic Chemistry, Faculty of Chemistry, University of Kashan) ;
  • Gandomi-Ravandi, S. (Laboratory of Organic Compound Research, Department of Organic Chemistry, Faculty of Chemistry, University of Kashan) ;
  • Ghotbinejad, M. (Laboratory of Organic Compound Research, Department of Organic Chemistry, Faculty of Chemistry, University of Kashan)
  • Received : 2011.07.27
  • Accepted : 2011.12.09
  • Published : 2012.02.20
Download PDF
⟨ Previous Next ⟩

Abstract

Aromatic 2,3-diazabuta-1,3-dienes in glacial acetic acid with isothiocyanate in the presence of catalyst $TiCl_4$ at room temperature produced via criss-cross cycloaddition reactions the corresponding perhydro[1,2,4]triazolo[1,2-a][1,2,4] triazole-1,5-dithiones in relatively high yields and short reaction time.

Keywords

INTRODUCTION

1, 3-Dipolar cycloaddition reactions are fundamental processes in organic chemistry,1 and their asymmetric version offers a powerful and reliable synthetic methodology to access five-membered heterocyclic rings in regio-and stereocontrolled fashion.2-5 Criss-cross cycloaddition was described in 1917 as intermolecular reaction of benzaldazine with 2 equiv of thiocyanate affording a heterocyclic compound having two fused five-membered ring.6 Criss-cross cycloaddition may be classified as a special type of [3+2] cycloaddition7 or 1, 3-Dipolar cycloaddition, respectively. The formation of their products was explained in 1963 by Huisgen8 as a success of two successive 1, 3-Dipolar cycloadditions. This assumption was proved in 1973 when as Table 1, 3-Dipole was identified by X-ray crystallographic analysis. 9 The 1, 3-Dipolar aldazine or ketazine are actually 1, 3-Heterodienes and have double 1, 3-Dipolar sites (Scheme 1).

These acyclic 1, 3-Heterodienes adopt the s-trans conformation due to steric interactions of the alkyl or aryl substations. This conformation dose not undergoes the [4+2] cycloaddition known as the Diels-Alder reaction. Azines as heterodiene reacted with two eqiv of dipolarophiles, such as thiocyanate, in [3+2] cycloaddition reactions and gave Perhydrotriazolotriazole derivatives.10-12

Meantime, it was found that this kind of compounds possesses many kinds of biological activities such as fungicidal, 13,14 bactericidal,13,14 analgesics,15-17 anxiolytic17 and anti-inflammatory.18

Scheme 1.Heterodienes containing double 1, 3-Dipolar sites.

 

RESULTS AND DISCUSSION

Main recent papers describing synthesis of perhydrotriazolotriazoles by classical method,19,20 but this method has defects such as long reaction times and low yield. Herein we report a facial and efficient method for the synthesis perhydrotriazolotriazoles catalyzed by TiCl4. In an initial study, for examination of the catalytic activity of different catalysts such as BF3, VCl3, WCl6, AlCl3, ZrCl4, SbCl3, Al2O3-P2O5 and TiCl4 in this cycloaddition reaction, benzaldazine was first reacted with potassium isothiocyanate in CH3CN (10 mL) in the presence of each catalysts (0.2 eqiv.) separately. In the course of this study we found that TiCl4 was the most effective catalyst in term of yield of the perhydrotriazolotriazoles (98%) while other catalysts formed the product with the yields of 46-88% (Table 1). In the absence of catalyst, the yield of the product was found to be very low (Table 2). All the products were characterized by NMR, IR and elemental alanalyses. The presence of signal at 1247-1293 cm-1 in IR spectra and 10.21-11.51 ppm in 1H NMR spectra, due to NH related to the fused five membered rings.

Table 1.aYields refer to the pure isolated product.

Table 2.aAll products were characterized by 1H NMR, 13C NMR, IR and element analysis. bIsolated yields

 

CONCLUSION

This work demonstrates a novel and highly efficient methodology for the synthesis of perhydrotriazolotriazoles from two successive 1, 3-Dipolar cycloadditon of azine derivatives and potassium isothiocyanate through TiCl4 catalyzed at room temperature. In addition of efficiency and simplicity, this protocol provides a fast and low cost procedure for the synthesis of these products.

 

EXPERIMENTAL

Instrumentation

Thin layer chromatography (TLC) was performed to monitor the reaction progress and purity of products. Melting points were measured using an electro thermal MK3 apparatus and are uncorrected. IR spectra were recorded using a Perkin-Elmer FT-IR 550 spectrometer in KBr pellets and reported in cm-1. NMR spectra were measured on a Bruker DRX 400 MHz spectrometer in DMSO-d6 with chemical shift (δ) given in ppm relative to TMS as internal standard. The element analysis (C, H, N) were obtained from a Carlo ERBA model EA 1108 analyzer carried out on Perkin- Elmer 240 c analyzers.

Reagents

All reactions were carried out at room temperature. Solvents and chemicals were purchased from Merck and used without prior purification. The compounds were prepared following reported procedure.

Recommended procedure

To mixture of KSCN (2.5 g, 0.0257 mol), CH3CN (10 mL) and aldazine (0.0128 mol) was added TiCl4 and the reaction mixture was stirred at room temperature for 20 min. the progress of the reaction was followed by TLC. After completion of the reaction, the suspension was poured in H2O (200 mL) and the mixture was concentrated in vacuo to remove the solvent. The resulting solid was washed successively with water. After dried in vacuum the product was obtained with enough purity for spectral analysis (Scheme 2).

Scheme 2.Preparation of perhydrotriazolotriazole derivatives catalyzed by TiCl4.

Tetrahydro-3, 7-diphenyl-[1,2,4] triazolo [1,2-a][1,2,4] triazole-1,5-dithione (3a, C16H14N4S2)

Yield: (97%) 3a. M.p.: 187-188 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.51, 1H NMR (400 MHz, DMSO): δ=6.82 (s, 2H, CH), 7.39 (t, 2H, CH), 7.41 (t, 2H, CH), 7.45 (t, 2H, CH), 11.42 (s, 2H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=73.02 (CH), 126.25 (CH), 127.76 (CH), 128.31 (CH), 129.73 (CH), 184.10 (C) ppm; IR (KBr): =3391, 1500, 1251 cm-1, Anal. Calcd. For C16H14N4S2 (326.433): C, 58.89%; H, 4.29%; N, 17.18%; S, 19.63%; Found: C, 58.82%; H, 4.39%; N, 17.34%; S, 19.73%.

3,7-Bis(4-chlorophenyl)-tetrahydro-[1,2,4]triazolo [1,2-a][1,2,4]triazole-1,5-dithione (3b, C16H12N4S2Cl2)

Yield: (91%) 3b. M.p.: 198-200 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.32; 1H NMR (400 MHz, DMSO): δ=6.85 (s, 1H, CH), 7.39 (dd, 1H, CH), 7.51 (dd, 1H, CH), 11.48 (s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=75.50 (CH), 128.41 (CH), 130.45 (CH), 133.20 (CH), 133.81 (CH), 184.11 (C), ppm; IR (KBr): =3410, 1490, 1248 cm-1, Anal. Calcd. For C16H12N4S2Cl2 (395.323): C, 48.60%; H, 3.04%; N, 14.18%; S, 16.20%; Cl, 17.72% Found: C, 48.32%; H, 3.13%; N, 14.31%; S, 16.29%; Cl, 17.81%

3,7-Bis(3-chlorophenyl)-tetrahydro-[1,2,4]triazolo [1,2-a][1,2,4]triazole-1,5-dithione (3c, C16H12N4S2Cl2)

Yield: (89%) 3c. M.p.: 194-195 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.31; 1H NMR (400 MHz, DMSO): δ=6.89 (s, 2H, CH), 7.16 (dd, 2H, CH), 7.37 (dd, 2H, CH), 7.42 (dd, 2H, CH), 7.49 (dd, 2H, CH), 11.50 (s, 2H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=76.62 (CH), 124.88 (CH), 126.39 (CH), 128.12 (CH), 134.15 (C), 184.47 (C), ppm; IR (KBr): =3415, 1500, 1252 cm-1, Anal. Calcd. For C16H12N4S2Cl2 (395.323): C, 48.60%; H, 3.04%; N, 14.18%; S, 16.20%; Cl, 17.72% Found: C, 48.32%; H, 3.13%; N, 14.31%; S, 16.29%.; Cl, 17.81%.

3,7-Bis(3-bromophenyl)-tetrahydro-[1,2,4]triazolo [1,2-a][1,2,4]triazole-1,5-dithione (3d, C16H12N4S2Br2)

Yield: (90%) 3d. M.p.: 158-159 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.38; 1H NMR (400 MHz, DMSO): δ=6.89 (s, 2H, CH), 7.41 (dd, 2H, CH), 7.42 (t, 2H, CH), 7.56 (t, 2H, CH), 7.62 (dd, 2H, CH), 11.51 (s, 2H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=74.01 (CH), 125.27 (C), 127.45 (CH), 127.79 (CH), 131.22 (CH), 132.61 (CH), 136.45 (C), 184.00 (C), ppm; IR (KBr): =3393, 1489, 1247 cm-1, Anal. Calcd. For C16H12N4S2Br2 (482.226): C, 39.85%; H, 2.51%; N, 11.62%; S, 13.30%; Br, 33.14% Found: C, 39.80%; H, 2.56%; N, 11.74%; S, 13.39%.; Br, 33.16%.

Tetrahydro-3,7-dimethyl-3,7-diphenyl-[1,2,4] triazolo [1,2-a][1,2,4]triazole-1,5-dithione (3e, C18H18N4S2)

Yield: (76%) 3e. M.p.: 118-119 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.42 1H NMR (400 MHz, DMSO): δ=2.29 (s, 6H, CH3), 7.38 (t, 2H, CH), 7.91 (t, 2H, CH), 8.27 (t, 2H, CH), 10.21 (s, 2H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=14.48 (CH3), 70.37 (C), 127.02 (CH), 128.71 (CH), 129.68 (CH), 138.08 (C), 179.41 (C), ppm; IR (KBr): =3405, 1588, 1291 cm-1, Anal. Calcd. For C18H18N4S2 (354.487): C, 61.02%; H, 5.08%; N, 15.82%; S, 18.08%; Found: C, 60.87%; H, 5.13%; N, 15.91%; S, 18.15%.

Tetrahydro-3,7-dimethyl-3,7-di(m-tolyl)-[1,2,4] triazolo [1,2-a][1,2,4]triazole-1,5-dithione (3f, C20H22N4S2)

Yield: (79%) 3f. M.p.: 159-160 ℃; RF/(ethyl acetate/n-Hexane) (3/7)=0.45; 1H NMR (400 MHz, DMSO): δ=2.27 (s, 6H, CH3), 2.33 (s, 6H, CH3), 7.19 (dd, 2H, CH), 7.68 (dd, 2H, CH), 7.76 (t, 2H, CH), 7.91 (t, 2H, CH), 10.18 (s, 2H, NH) ppm; 13C NMR (100 MHz, DMSO): δ=24.6 (CH3), 28.9 (CH3), 76.2 (C), 124.01 (CH), 127.01 (CH), 128.51 (CH), 128.80 (CH), 138.21 (C), 142.42 (C), 183.51 (C), ppm; IR (KBr): =3386, 15878, 1293 cm-1, Anal. Calcd. For C20H22N4S2 (382.540): C, 62.83%; H, 5.67%; N, 14.66%; S, 16.75%; Found: C, 62.77%; H, 5.84%; N, 14.81%; S, 16.87%.

References

  1. Padwa, A. Vol. 2; Wiley: New York, 1984; p 277.
  2. Harwood, L. M.; Vickers, R. J. Wiley: New York, 2002, p 169.
  3. Gothelf, K. V.; Jorgensen, K. A.; Kobayashi, S. Wiley-VCH: Weinheim, 2002; p 211.
  4. Karlsson, S.; Hogberg, H. E. Org. Prep. Proceed. Int. 2001, 33, 103. https://doi.org/10.1080/00304940109356583
  5. Najera, C.; Sansano, J. M. Curr. Org. Chem. 2003, 7, 1105. https://doi.org/10.2174/1385272033486594
  6. Bailey, J. R.; Moor, N. H. J. Am. Chem. Soc. 1917, 39, 279. https://doi.org/10.1021/ja02247a011
  7. Bailey, J. R.; McPherson, A. T. J. Am. Chem. Soc. 1917, 39, 1322. https://doi.org/10.1021/ja02252a006
  8. Huisgen, R. Angew. Chem., Int. Ed. Engl. 1963, 2, 565. https://doi.org/10.1002/anie.196305651
  9. Gieren, A.; Narayana, P. P.; Burger, K.; Thenn, W. Angew. Chem., Int. Ed. Engl. 1974, 13, 475. https://doi.org/10.1002/anie.197404751
  10. Burger, K.; Thenn, W.; Rauh, R.; Schickaneder, H. Angew. Chem., Int. Ed. Engl. 1974, 13, 477. https://doi.org/10.1002/anie.197404771
  11. Burger, K.; Schickaneder, H.; Thenn, W. Tetrahedron Lett. 1975, 16, 1125. https://doi.org/10.1016/S0040-4039(00)72075-2
  12. Evans, S.; Gearhart, R. C.; Schweizer, E. E. J. Org. Chem. 1977, 42, 452. https://doi.org/10.1021/jo00423a014
  13. Deshpande, D. S. Chem. Abstr. 1985, 94, 65568.
  14. Paget, C. J.; Wikl, J. H. Chem. Abstr. 1976, 84, 44070.
  15. Kamal, A.; Sattur, P. B. Chem. Abstr. 1985, 102, 166690.
  16. Morogues, J.; Vega, A.; Prieto, J.; Marquez, M. Roberts, D. J. Chem. Abstr. 1976, 84, 180138.
  17. Prasad, A. R.; Ramalingam,T.; Rao, A. B. Diwan, P. V.; Sattur, P. B. Chem. Abstr. 1987, 106, 84500.
  18. Moran, D. B.; Dusza, J. P. Albright, J. D. Chem. Abstr. 1981, 95, 97829.
  19. Zachova, H.; Man, S.; Taraba, J.; Potacek, M. Tetrahedron 2009, 65, 792. https://doi.org/10.1016/j.tet.2008.11.057
  20. Verner, J.; Potacek, M. Molecules 2006, 11, 34. https://doi.org/10.3390/11010034

Cited by

  1. An efficient synthesis of perhydro[1,2,4]triazolo[1,2-a][1,2,4]triazole-1,5-dithiones catalyzed by TiO2-functionalized nano-Fe3O4encapsulated-silica particles as a reusable magnetic nanocatalyst vol.5, pp.127, 2015, https://doi.org/10.1039/C5RA23457C
  2. Structure, synthesis and application of azines: a historical perspective vol.4, pp.86, 2014, https://doi.org/10.1039/C4RA04870A
  3. The π–π interactions enhanced in salicylaldimines and salicylaldazines vol.71, pp.40, 2015, https://doi.org/10.1016/j.tet.2015.07.049
  4. One Step Synthesis of Symmetrical Amino Azine Derivatives Using Hydrazine Hydrate as a Reagent vol.840, pp.None, 2012, https://doi.org/10.4028/www.scientific.net/kem.840.257
  5. Synthesis of Triazolothiones Using Nano-Fe3O4@SiO2-SO3H as a Heterogeneous Catalyst vol.52, pp.5, 2020, https://doi.org/10.1080/00304948.2020.1780885