Tetrabutylammonium bromide (TBAB) a facile phase transfer catalyzed direct synthesis of α, α-dihalo methyl sulfones

Authors

• Suryakiran Navath Department of pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201 USA.

Abstract

Tetrabutylammonium bromide (TBAB) a facile phase transfer catalyzed direct synthesis of α, α-dihalo methyl sulfones by the reaction of sodium alky/ aryl sulphinate with halofom is described. Obtained products were purified with column chromatography and crystallization and all products were characterized by ¹H NMR and mass spectral data

Abstract

Tetrabutylammonium bromide (TBAB) a facile phase transfer catalyzed direct synthesis of α, α-dihalo methyl sulfones by the reaction of sodium alky/ aryl sulphinate with halofom is described. Obtained products were purified with column chromatography and crystallization and all products were characterized by ¹H NMR and mass spectral data

Introduction

Sulfones are of great importance in organic synthesis, among them -halo methyl aryl/ alkyl sulfones, , -dihalo methyl alkyl/ aryl sulfones are excellent -carbanion-stabilizing substituents,¹ they are precursors for the preparation of alkenes,² aziridines,³ and epoxides,⁴ Makosza⁵ have been utilized chloromethyl phenyl sulfones and chloromethyl p-tolyl sulfones in vicarious nuclephilic substitution (VNS) reactions with nitro arenes to afford VNS adducts. These adducts have been elaborated into both 3-sulfonyl substituted indole derivatives and the analogues indazoles.⁶ Halo alkyl sulfones are useful preventing aquatic organisms from attaching to fishing nets and shiphulls,⁷ in herbicides compositions,⁸ bactericidal,⁹ anti fungal,^[10] algaecides,^[11] and insecticides.¹² All though the methods of synthesis of -halo methyl sulfones and , -dihalo methyl sulfones have been reported in literature,^13-17 but not explored much. Now we wish to report a facile phase transfer catalysed direct synthesis of -halo methyl sulfones and , -dihalo methyl sulfones.

Typically, one or more of the reactants are organic liquids or solids dissolved in a nonpolar organic solvent and the coreactants are salts or alkali metal hydroxides in aqueous solution. Reactions between these substances which are located partly in an organic phase and partly in an aqueous phase are usually very slow. Employing nonpolar organic solvents alone frequently leads to heterogeneous reaction mixtures and the use of polar, aprotic solvents like DMSO, DMF, etc. under elevated reaction temperature conditions to achieve homogeneous solutions increases both the cost and the difficulties encountered in the work-up procedures. The use of alcoholic solvents to maximize the solubility of both reactants usually leads to slow reaction rates owing to extensive solvation of the anions, and reactions of the nucleophilic solvent complicate the product mixtures. A Phase-transfer catalysis (PTC) is a technique by which reactions between substances located in different phases are brought about or accelerated.

Scheme 1.

A phase-transfer catalyst is a catalyst that facilitates the migration of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic reactants are often soluble in an aqueous phase but insoluble in an organic phase in the absence of the phase-transfer catalyst. The catalyst functions like a detergent for solubilizing the salts into the organic phase. Phase-transfer catalysis refers to the acceleration of the reaction upon the addition of the phase-transfer catalyst. By using a PTC process, one can achieve faster reactions, obtain higher conversions or yields, make fewer byproducts, eliminate the need for expensive or dangerous solvents that will dissolve all the reactants in one phase, eliminate the need for expensive raw materials and/or minimize waste problems¹⁸. Phase-transfer catalysts are especially useful in green chemistry by allowing the use of water, the need for organic solvents is reduced.^19-20

Results and Discussions

Reaction of halo form 2 with sodium aryl / alkyl sulphinate salt¹⁸ 1 refluxing with aqueous alkali for 12 hrs results in the formation of , - dihalo methyl sulfones 3 in about 7-60% yield. However by using of TBAB as PTC in acetonitrile as reaction medium, the product in over 90% yield in one hour. In order to optimize the reaction conditions changing the solvents Table 1, temperature and type of phase transfer catalysts (TBAB, TEBAC, TBAI). It has been observed best results are obtained by refluxing the reaction mixture in acetonitrlle by using of TBAB as phase transfer catalyst a,a-dihalo methyl p-toluene sulfone in 90% yield. The poor yield in case of hydroxylic solvents and less polar solvents are probably due to the lower solubility of the sulphinate salt in the solvents. The phase transfer catalyst, apart from increasing the solubility of 1 in the solvents, increases the effectiveness of the nucleophile.

Table 1: Solvent effect on the reaction of sodium p-toluenesulphinate with Chloroform and TBAB as phase transfer catalyst under reflux conditions

Using optimum conditions, different types of -halo methyl sulphones, , -dihalo methyl sulphones, have been synthesized in facile manner (Table 2). In the course of our study, the sodium alkyl/ aryl sulphinate salt having reductive dehalogenating nature. So, making it likely that product formation takes place by reductive dehalogenation of halo form, di halo methane followed by nucleophilic attack of sulphinate sulphur. In the case of sodium t-butyle sulphinate on prolonged heating with halo form, mixer of mono halo, dihalo methyle sulfone was observed. It may be due to reductive de halogenation of dihalomethylesulfone by sodium t-butyl sulphinate. The product formation was not achieved with sodium methyl sulphinate and sodium benzyl sulphinate because it known to form Ramberg backlind rearrangement¹⁹after formation of α, α-dihalo methylsulfonesulfone. The products has been characterized by its spectral data and by its alternative chemical method, the latter was achieved by reaction of sodium sulfinate salt with -halo ketone yilds, -keto sulfone, it is on halogenation, follwed by base induced cleavage of α, α-dihalo alkyl/ aryl sulfonyl acetophenone¹⁷ with aqueous alkali gave the corresponding product.

TBAB + NaOH TBAOH + NaBr

TBAOH + CHCl₃ :CCl₂ + H₂O

Scheme 2. Plausible Mechanism

In conclusionwe described a facile direct synthesis of different types of , -dihalomethyl sulphones, on the reaction of sodium alkyl aryl sulphinate with chloroform and bromoform in the presence of catalytic amount of phase transfer catalyst.

Acknowledgements

The authors are thankful to CSIR and DOD, New Delhi for financial assistance and Director IICT for his constant encouragement.

Typical Experimental procedure

A mixture of sodium alkyl/ aryl sulphinate (10 mmol) haloform (15 mmol) and NaOH (10 mmol) was taken in 20 ml of acetonitrile refluxed in the presence of TBAB for appropriate time (Table 2) then extracted into ethyl acetate solvent was evaporated under reduced pressure crude product was purified by silica column chromatography. Dichloromethyl p-tolyl sulfone (1). M.p. 89-90.5⁰C. ¹HNMR (CDCl₃): 2.5 (3H, s), 6.25 (1H, s), 7.4 (2H, d), 7.81 (2H, d), MS (EI) m/z:139(M^+.). Dichloromethyl phenyl sulfone (2). M.p. 79-80⁰C. ¹HNMR (CDCl₃): 6.20 (1H, s), 7.45 (2H, d), 7.65 (1H, m) 7.99 (2H, d), MS (EI) m/z:225(M^+.). Dibromomethyl p-tolyl sulfone (3). M.p. 115⁰C. ¹HNMR (CDCl₃): 2.5 (3H, s), 6.19 (1H, s), 7.4 (2H, d), 7.8 (2H, d), MS (EI) m/z:328(M^+.). Dibromomethyl phenyl sulfone (4). M.p. 112⁰C. ¹HNMR (CDCl₃): 6.18 (1H, s), 7.4 (2H, d), 7.7 (1H, m) 7.9 (2H, d), MS (EI) m/z:312(M^+.).

Table 1. Synthesis of , -dihalo methyl sulfones using phase transfer catalyst. Isolated yields after column chromatography / crystallization and all products gave satisfactory spectral and analytical data

References

1. Simpkins, N. S. Sulfones in organic synthesis; Ed. Baldwin, J. E. Pergamon press: oxford, 1993.b) Jonczyk, A.; Banko, K.; Makoza, M. J. Org. Chem. 1975, 40, 266.
2. Lee, J. W.; Oh, D. Y. S. Synth. Commun. 1990, 20, 273. b) Bardwell, F. G.; Coopert, G. D.J. Am. Chem. Soc. 1951, 73, 5184.
3. Reutrakal, V.; Prapansiri, V.; Panyachotipun, C.Tetrahedron lett. 1984, 25, 1949.
4. Adamczy, K. M.; Dolence, E. K.; Watt, D. S.; Christy, M. R.; Reibenspies, J. H.; Anderson, O. P. J. Org. Chem. 1984, 49, 1378. b) Dolence, E. K.; Adamczy, K. M.; Watt, D. S.; Rasell, G. B.; Horn, D. H. S. Tetrahedron lett. 1985, 26, 1189. c) Arai, S.; Ishidu, T.; Shioiri, T. Tetrahedron lett. 1998, 39, 8299. d) Nagashima, E.; Suzuki, K.; Ishikawa, M.; Sekiya, M. Heterocycles, 1985, 23, 1873.
5. Golinski, J.; Makosza, M. Tetrahedron lett. 1978, 37, 3495. b) Makosza, M.; Chylinska, B.; Mudryk, B. Ann. Chem. 1984, 1, 8. c) Wojciechowski, K.; Makosza, M. Tetrahedron lett. 1989, 62, 4793. d) Wojciechowki, K.; Makosza, M.Synthesis 1986, 8, 651.
6. Takhashi, M.; Suga, D. Synthesis, 1998, 7, 986.
7. Oishi, Y.; Watanabe, T.; Kusa, K.; Kazama, M.; Koniya, K. 1988, JP. October 7, 63, 243, 067.
8. Shigematsy, S.; Yamada, Y.; Kimura, I. Herbicidal composition for Rice. July 30, 1983, JP 58, 128, 305.z
9. Baker, F. C.; Li, J. P. N. Substituted male imides in liquid concentrates, January 27, 1981, US 4, 247, 559.
10. Eckstein, Z.; Zavistowska, M.; Palut, D.; Polubiec, E. Aromatic derivatives of chloromethyl sulfones, Pol. J. Chem. 1966, 45, 314.
11. Ejmocki, Z.; Krassowska, B. K.; Olezak, I.; Eckstein, Z. Pol. J. Chem. 1980, 54, 11-27 and 2153 – 2159.
12. Antane, S.; Bernotas, R.; Li, Y.; David. Mc. R.; Yan, Y.; Synth. Commun. 2004, 34, 2443.
13. Middlebos, W.; Strating, J.; Zwanenberg, B. Tetrahedron Lett. 1971, 12, 351
14. Ziegler, W. M.; Conner, R. J. Amer. Chem. Soc. 1940, 62, 2596.
15. Barr, E.; Ziegler, W. M.; Conner, R. ibd. 1941, 63, 106.
16. Kresze, G.; Schram, W. M.; Cleve, G. Chem. Ber. 1961, 94, 2060.
17. Grossert, J. S.; Dubey, P. K.; Gill, G. H.; Cameron, T. S.; Gardner, P. A. Can. J. Chem. 1984, 62, 174.
18. Vogel’s Textbook of practical organic chemistry, 5 th edition p 888.
19. Rigby, J. H.; Warshakoon, N. C. J. Org. Chem. 1996, 61, 7644.
20. Katole, D. O.; Yadav, G. D. Mol. Cat. 2019, 466, 112.
21. Metzger, J. O. Ang. Chem. Int. Ed. 1998, 37, 2975–2978.
22. Makosza, M. Pure Appl. Chem. 2000. 72, 1399–1403.