A simple and efficient synthesis of 2-(2-(Methylthio)phenyl)-3,4-dihydro-2H-pyrrole

 

Ajay Kumar R, Dayakar G*

Department of Chemistry, Kakatiya University, Vidyaranyapuri, Hanamkonda,

Warangal-506009, Telangana, India

*Corresponding Author E-mail: gadedayakar@yahoo.co.in

A simple and efficient synthesis of A simple and efficient synthesis of 2-(2-(methylthio)phenyl)-3,4-dihydro-2H-pyrrole is carried out using trichloroacetic acid from  tert-butyl (4-(2-(methylthio)phenyl)-4-oxobutyl)carbamate (2). The structures of the compounds are confirmed by ¹H NMR and LC Mass analyses.

 

 

 

INTRODUCTION:

For several decades, interest in pyrrole derivatives as antimicrobial agents has led to the preparation and antimicrobial evaluation of hundreds of such molecules. For example, monodeoxypyoluteorin and 2-(2'-hydroxybenzoyl) pyrrole bromine derivatives are pyrrole derivatives having antimicrobial activity^1,2. 3,4,5,3,5-Pentabromo--2-(2-hydroxybenzoyl)pyrrole, a synthetic antibacterial compound related to pyrrolomycins, has significant activity³. 2-Methyl-1,3,5-trisubstituted pyrroles have significant activity^4,5. Diguanidino-1-methyl-2,5-diaryl-1H-pyrrole derivatives have antifungal activity against Candida species⁶. Tubercidin, toyocamycin and sangivamycin are naturally occurring pyrrolo[2,3-d]pyrimidine antibiotics having significant activity against Mycobacterium tuberculosis, Candida albicans and Streptococcus neoformans, which was shown in many reports^7-9.

 

In this communication we report a facile synthesis of 2-(2-(methylthio)phenyl)-3,4-dihydro-2H-pyrrole, hoping that they could be of promising chemical and biological interest.

 

Experimental:

Chemicals and solvents were reagent grade and used without further purification. Melting points were determined on a capillary melting point apparatus and are uncorrected. The ¹H NMR spectra were recorded in the indicated solvent on a Varian 400 MHz spectrometer with TMS as internal standard. All chemical shifts (ä) were reported in ppm from internal TMS. Mass spectra were measured on a Jeol JMS D-300 spectrometer. The homogeneity of the compounds was checked using precoated TLC plates (E. MerckKieselgel 60 F₂₅₄).

 

 

 

 

 

Scheme:

 

Synthesis of tert-butyl (4-(2-(methylthio)phenyl)-4-oxobutyl)carbamate (2):

To a stirred solution of (2-bromophenyl)(methyl)sulfane (1) (2.81 mmol) in THF (5 mL) was added t-BuLi (3.24 mmol) at -78 °C and stirred for 45 min. A solution of tert-butyl 2-oxopyrrolidine-1-carboxylate ( 2.16 mmol) in THF (5 mL) was added to the reaction mixture at -78 °C and stirring was continued for another 2 h. The resulting reaction mixture was allowed to warm to room temperature and stir for 14-18 h. The reaction mixture was quenched with aqueous NH₄Cl and extracted with EtOAc. Organic layer were washed with water, dried over sodium sulphate, filtered and concentrated to obtain the crude product. The crude material was purified by silica gel column chromatography to afford compound 2 (58%) as white solid.

 

¹H-NMR (DMSO-d₆, 400 MHz): ä 7.94 (d, 1H), 7.56 (t, 1H), 7.44 (d, 1H), 7.24 (t, 1H), 6.86 (br s, 1H), 2.96-2.92 (m, 2H), 2.36 (s, 2H), 1.76 (t, 2H), 1.39 (s, 12H);

 

Synthesis of 2-(2-(methylthio)phenyl)-3,4-dihydro-2H-pyrrole(3):

To a stirred solution of compound 2 (1.29 mmol) in CHCl₃ (10 mL) was added TCA (1.0 mL) at 0 °C under N₂ atmosphere. The resultant reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was quenched with saturated NaHCO₃ and extracted with CHCl₃. The combined organic layer was washed with water (10 mL) and dried over sodium sulphate, filtered and concentrated to obtain the crude product. The crude material was purified by silica gel column chromatography to afford compound 3 (53%) as an off-white solid.

 

¹H-NMR (DMSO-d₆, 400 MHz): δ 7.54 (d, 1H), 7.42-7.37 (m, 2H), 7.20-7.16 (m, 1H), 4.01 (t, 2H), 2.96 (t, 2H), 2.34 (s, 3H), 1.96-1.87 (m, 2H);

LC-Mass: 97.11%; 192.2 (M+H);

 

 

REFERENCES:

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9.     Rao K. V., Structure of sangivamycin, J. Med. Chem. 11 (1968) 939.

 

 

 

 

Received on 06.01.2018         Modified on 28.03.2018

Accepted on 20.04.2018         © AJRC All right reserved