MCM-41 (H) Catalyzed Selective Deprotection of Sulfonamides

 

Prasad Gundepaka^1,3, Sarangapani Modam², Mukkanti Kagga¹, Shravankumar Kankala²*, Ravinder Vadde²*,  Chandra Sekhar Vasam³*

¹Centre for Pharmaceutical Science, Institute of Science and Technology, JNTU, Hyderbad, India.

²Department of Chemistry, Kakatiya University, Warangal, India -506 009,

³Department of Chemistry, Satavahana University, Karimnagar, India-505 001,

*Corresponding Author E-mail: shravankankala@yahoo.com, vasamcs@yahoo.co.in

 

A facile and efficient method for the selective deprotection of sulphonamides has been achieved for the first time using MCM-41 (H) Zeolite. The procedure is applicable to a wide variety of sulphonamides and the catalyst can be recyclable and reusable is described.

 

 

INTRODUCTION:

Zeolites promoted reactions are advantageous in many ways over conventional approaches, especially due to shorter times, the routine cleanliness of the processes and simple work up procedures. For a long time, aromatic sulphonic acids have been used in the derivatization of amines and the protection of amino functions ^l and the resultant crystalline sulphonamides are very resistant to nucleophillic attack. Recently, the use of inorganic solid supports as catalysts have been developed for dry media reactions² resulting in higher selectivity, milder conditions and ease of handling. Toluenesulfonyl groups are widely used as protecting agents for hydroxyl groups^3,4 and amines¹. These groups are highly stable and require drastic deprotection conditions.

 

In the literature, a limited number of methods are available for the cleavage of sulphonamides utilizing a variety of reagents such as sodium in liquid ammonia⁴, sodium naphthanilide⁵ or Mg-MeOH⁶ and hydrogenolysis with Nickel⁷ and KF-Al₂O₃ under microwave irradiation⁸. Furthermore, aryl toluene sulphonamides are more stable than alkyl toluene sulphonamides and require refluxing aqueous alcoholic KOH for their deprotection.

 

EXPERIMENTAL:

General:

All commercially available reagents were used without further purification.  Reaction solvents were dried by standard methods before use. Purity of the compounds was checked by TLC using Merck 60F254 silica gel plates. Elemental analyses were obtained with an Elemental Analyser Perkin-Elmer 240C apparatus. ¹H and ¹³C NMR spectra were recorded with a Mercuryplus 200 spectrometer (operating at 200 MHz for ¹H and 50 MHz for ¹³C); chemical shifts were referenced to TMS. EI (electron impact) mass spectra (at an ionising voltage of 70 eV) were obtained using a Shimadzu QP5050A quadrupole-based mass spectrometer.

 

General procedure for the selective cleavage of tosyl group⁹:

A mixture of N-tosyl-pinidine (1.0g, 1 mmol), and MCM-41 (H) (0.5 g) in acetonitrile (10 mL) was heated at reflux for 1 h. The reaction mixture was allowed to cool room temperature, and was extracted with dichloromethane (2 x 20 mL). The combined organic layers were dried (anhydrous Na₂SO₄) and evaporated under reduced pressure to afford a crude product which was subjected to column chromatography (silica gel, 60-120 mesh, eluent; n-hexane/EtOAc gradient) to afford pure products (2k).

 

Compound (2k): white crystalline solid ¹H NMR (200 MHz, CDCl₃): δ = 0.98-1.20 (m, 2H), 1.05 (d, 3H), 1.28-1.40 (m, 2H), 1.54-1.59 (m, 2H), 1.65 (d, 3H), 1.74-1.78 (m, 1H), 2.62-2.68 (m, 1H), 3.02-3.05 (m, 1H), 5.45 (ddd, 1H), 5.56 (dq, 1H) ppm. ¹³C NMR (50 MHz, CDCl₃): δ = 18.02, 23.24, 24.80, 32.41, 34.05, 52.35, 59.60, 125.02, 135.36 ppm. MS (EI, 70 eV): m/z (%) = 162 [M+Na]⁺. EA calcd (%) for C₉H₁₇N: (139.14): C 77.63, H 12.31, N 10.06; found C 77.62, H 12.30, N 10.02.

 

RESULTS AND DISCUSSION:

In this article, we wish to report a simple and efficient deprotection method for sulphonamides using MCM-41 (H) Zeolite.^10–12 (Scheme 1).

 

This method is general and applicable for the cleavage of aryl as well as alkyl toluene sulphonamides (See Table 1). Reductive cleavage of sulphonamides with SmI₂¹³, Mg/MeOH, Na/liquid ammonia and Sodium/napthalide results in the reduction of the other functional groups such as halides, nitro, azide, carbonyl and a,b-unsaturated systems.¹⁴ The use of HBr/AcOH¹⁵ is highly acidic and it does not tolerate acid sensitive functionalities like Boc, Cbz and ethers. Na in liquid ammonia affords low yields associated with cumbersome experimental and tedious isolation procedures. Present reaction conditions have been shown to be compatible with a range of these functional groups (Table 1). An advantage over existing methodologies was achieved by MCM-41 (H) zeolite, wherein the products were obtained in 78-95%. Important features of the reaction are that the MCM- 41(H) zeolite was recovered and reused for four cycles without substantial loss in the yields.

 

Scheme 1. Deprotection of sulfonamides using MCM-41 (H) zeolite.

 

Table 1. Deprotection of sulfonamides to amines using MCM-41 (H)^a

 

 

CONCLUSION:

In conclusion, we have developed a simple, convenient and efficient method for the deprotection of sulfonamides. This method offers significant advantages such as improved yields, operational simplicity, shorter reaction times and easy workup.

 

ACKNOWLEDGEMENTS:

The one of authors PG thanks to Innogent Laboratories Pvt. Ltd and Dr. S. Kankala thanks CSIR, New Delhi for the award of Research Associate.

 

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Received on 02.10.2013          Modified on 01.11.2013

Accepted on 04.11.2013         © AJRC All right reserved