INTRODUCTION:

Carbazole is a tricyclic compound with the carbon skeleton of fluorene, occurring in coal tar. Due to its fluorescent properties, carbazole ring system is a structural element of many compounds used in electronics for the production of electroluminescent materials polymers or dyes. Very interesting biological properties of active carbazole alkaloids^1,4, isolated mainly from taxonomically similar plants of the genus Murraya, Glycosmis and Clausena in the family Rutaceae caused that many research groups became interested in the structural modifications of natural compounds and synthesis of new derivatives of carbazole⁷

There are known biologically active fused aromatic systems of natural origin (alkaloids) or synthetic drugs containing in their structure an element of carbazole as well as derivatives of tricyclic carbazole³, which possess anti-cancer⁶, antibacterial, antifungal, anti-inflammatory, hepatoprotective, anti-HIV, antiprotozoan and sedative properties, or topoisomerase II inhibition ability.¹⁰

EXPERIMENTAL PROCEDURE:

All the commercially available reagents were used without further purification. The purity of the compound was checked by TLC using All reactions are monitored by thin layer chromatography (TLC) carried out on 0.25 mm E. Merck silica gel plates (60F-254) with UV light, iodine as probing agents. Acme (India) silica gel (finer than 200 mesh) is used for flash chromatography. ¹H and ¹³C NMR were recorded with a mercury plus spectrometer (operating for 250 MHz for ¹H AND 50MHz for ¹³C); chemical shift were referenced to TMS. IR spectra were recorded with Perkin-Elmer881 spectrometer. Mass spectra were recorded on Micro Mass VG-7070H mass spectrometer for EI.

General procedure for the synthesis of Carbazole linked propeonones:

STEP-1: Synthesis of N-methyl Carbazole:^2,9

To a 250 mL round bottom flask containing 20 ML of dichloromethane, 1.5 Eq of Methyl Iodide (CH3I) and Potassium Hydroxide (KOH) were added one after the other. After stirring the above mixture for 15 minutes, Carbazole 1 Eq was added to the round bottom flask and the reaction was allowed to stirr at room temperature and was monitored by Thin layer Chromatography. To a 250 mL round bottom flask containing 20 ML of dichloromethane, 1.5 Eq of Methyl Iodide (CH3I) and Potassium Hydroxide (KOH) were added one after the other. After stirring the above mixture for 15 minutes, carbazole 1 Eq was added to the round bottom flask and the reaction was allowed to stirr at room temperature and was monitored by Thin layer Chromatography.

STEP-2: Procedure for Acylation of N-methyl Carbazole (CAM) to get Acylated N methyl Carbazole (CAM) (Via Freidel craft’s Acylation)⁸

To a 250 ML Round bottom flask, 1.5 Equivalents of Acetyl chloride and 1.5 Equivalents of Anhydrous Aluminium Chloride were added at 0^oC in Dichloro Methane solvent (20mL). After stirring for few minutes, (CAM) was dissolved in sufficient quantity of Dichloromethane and was added drop wise to the above Stirring mixture Maintained at 0^OC. The reaction was allowed to stirr at room temperature for 4 hours and was monitored by Thin layer Chromatography. After the completion of the reaction, the reaction mixture was quenched with water to remove traces of Aluminum Chloride. Later the reaction mixture was extracted with water and Dichloromethane (3*20mL). The organic layer was collected, dried over sodium sulphate and evaporated to dryness to obtain a Yellow solid which was recrystaliised by Ethyl acetate/Hexane system and purified by Column chromatography using Ethyl acetate/Hexane Solvent system (3:7 ratio).

Step-3: Procedure for Synthesis Of Novel Carbazole linked Propeonone Conjugates (Clasien Condensation reaction)⁵.

The Acylated N-methyl carbazole (1Eq) which was obtained in the previous step was added in a 100mL one necked round bottom flask in 10mL of Methanol. Substituted Benzaldehyde (1Eq) was added to the above stirring mixture and the reaction was allowed to stirr at room temperature for 10mins. After this, Barium Hydroxide (base, 5Eq) was added slowly to the round bottom flask. The color of the reaction mixture starts to change soon after the addition of the base. The reaction was monitored at room temperature for 5 hours by means of Thin Layer Chromatography. The reaction mixture was washed with water extracted witty ethyl acetate (3*20mL). The organic layer was collected, dried over sodium sulphate and evaporated to dryness to obtain a Yellowish solid which was recrystaliised by Ethyl acetate/Hexane system and purified by Column chromatography using Ethyl acetate/Hexane Solvent system (3:7). All the compounds (4a-4i) were prepared in a similar manner.

SPECTRAL ANALYSIS OF COMPOUNDS:

R-C₆H₅CHO:

Cam-a, R= (OCH₃)₃- C₆H₅CHO, Cam-b, R=CN- C₆H₅CHO, Cam-c, R=p-Cl- C₆H₅CHO, Cam-d, R=p-F-C₆H₅CHO,Cam-e, R=OCH₃ C₆H₅CHO, Cam-f, R=CF₃-C₆H₅CHO, Cam-g, R=CN- C₆H₅CHO, Cam-h, R=m-Cl- C₆H₅CHO, Cam-i, R=m-F- C₆H₅CHO

Characteristics of New Carbazole Linked Propeonones (Cam-a, Cam-b, Cam-c, Cam-d, Cam-e, Cam-f, Cam-g, Cam-h, Cam-i)

Cam-A:

4-[(1E)-3-(9-methyl-9H-carbazol-3-yl)-3-oxoprop-1-en-1-yl] 3, 4, 5 trimethoxy benzene, MP: 46.3°C. NMR: δ : 3.92 (s, 6H,-OCH3), 3.956 (s, 6H,-OCH3), 6.93 (s, 2H, ArH), 7.30-7.34 (m,1H,Ar-H),7.45-7.48 (m, 2H, ArH), 7.52-7.56 (m, 1H, ArH), 7.60-7.69 (d,1H, ArH, J=15.52), 7.79-7.83 (d,1H, ArH, J=15.52), 8.18-8.25 (m, 2H, Olefinic-H), 8.89 (s, 1H, ArH).IR: C-O-C 1024.45, C=O 1670.12, Ar C-H(str) 1141.92, Ar C-N 1321.05

Cam-B:

4-[(1E)-3-(9-methyl-9H-carbazol-3-yl)-3-oxoprop-1-en-1-yl]benzonitrile, M.P:44.3°C NMR: δ : 3.83 (s, 3H,-NCH3), 7.32-7.33 (m, 1H, ArH), 7.45 (d, 2H, J=8.43 ArH), 7.52-7.54 (m, 1H, ArH), 7.79-7.80 (m, 4H, ArH), 7.82 (s, 2H, Ar-H) 8.18-8.21.(m, 2H, Ar-H), 8.81 (s, 1H, Olefinic-H).IR: Ar C-H(str) 1141.92. Ar C=C 1487.85, C=O 1670.12, CN 2220.23, Ar C-N 1321.05

Cam-C:

(2E)-3-(4-chlorophenyl)-1-(9-methyl-9H-carbazol-3-yl)prop-2-en-1-one, MP: 36.8°C NMR: δ 3.84 (s, 3H,-NCH3), 7.30-7.31 (m, 1H, ArH), 7.40-7.42 (m, 4H ,ArH), 7.52 (m, 1H, ArH), 7.68 (d, 2H, J=8.64, ArH), 7.71 (d,1H, J=15.7,Olefinic H), 7.82 (d,1H, J=15.7,Olefinic H), 8.18 (m, 2H, Ar-H), 8.78 (s, 1H, ArH). IR: C-Cl 751.07, ArC-H (str) 1074.77, Ar C=C 1598.73, C=O 1670.12

Cam-D:

(2E)-3-(4-fluorophenyl)-1-(9-methyl-9H-carbazol-3-yl)prop-2-en-1-one, MP:32.4°C NMR: δ 3.87 (s, 3H,-NCH3), 6.97-7.06 (m, 2H,ArH), 7.10-7.14 (m, 1H, ArH), 7.30-7.34 (m, 2H, ArH), 7.41-7.43 (m, 1H ,ArH), 7.51 (m, 2H, ArH), 7.66-7.69 (m, 2H, ArH), 7.83 -7.84 (m,1H, ArH), 8.16 (d, 1H, J=16.64, ArH), 8.22 (d, 1H, J=23.01, Olefinic H). IR: C-F 1064.04 Ar C=C 1601.57,Ar C-H 830.77, Ar C-N 1359.32.

Cam-E:

(2E)-3-(4-methoxyphenyl)-1-(9-methyl-9H-carbazol-3-yl)prop-2-en-1-one, MP: 38.8°C NMR: 500 Hz (CdCl3) δ : 3.92 (s, 9,-OCH3), 6.93 (s, 2H, ArH), 7.30-7.34 (m,1H,Ar-H),7.45-7.48 (m, 2H, ArH), 7.52-7.56 (m, 1H, ArH), 7.60-7.69 (d,1H, ArH, J=15.52), 7.79-7.83 (d,1H, ArH, J=15.52), 8.18-8.25 (m, 2H, Olefinic-H), 8.89 (s, 1H, ArH). IR: C-O-C 1054.18, Ar C=C 1604.25, ArC-H(str) 1206.47,ArC-H(bending) 811.53

Cam-F:

(2E)-1-(9-methyl-9H-carbazol-3-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one MP: 28.4°C NMR: 3.91 (s, 3H,-NCH3), 7.32-7.33 (m, 1H, ArH), 7.47 (m, 4H, ArH), 7.55 (m, 2H, ArH), 7.61 (d, J=7.77, 1H, ArH), 7.79. (d, J=15.77, 1H, Olefinic H), 7.82 (d, 1H, J=15.61, Ar-H) 8.23.(m, 2H, Ar-H), 8.84 (s, 1H, Olefinic-H) IR: C-F 1063.21, Ar C=C 1600, Ar C-H 1025.01, Ar C-N 1321.05.C=O 1680.32

Cam-G:

3-[(1E)-3-(9-methyl-9H-carbazol-3-yl)-3-oxoprop-1-en-1-yl]benzonitrile. MP: 40.1°C NMR: δ : 3.83 (s, 3H,-NCH3), 7.32-7.33 (m, 1H, ArH), 7.45 (d, 2H, J=8.43 ArH), 7.52-7.54 (m, 1H, ArH), 7.79-7.80 (m, 4H, ArH), 7.82 (s, 2H, Ar-H) 8.18-8.21.(m, 2H, Ar-H), 8.81 (s, 1H, Olefinic-H). IR: Ar C-H(str) 1141.92. Ar C=C 1487.85, C=O 1670.12, CN 2220.23, Ar C-N 1321.05

Cam-H:

(2E)-3-(3-chlorophenyl)-1-(9-methyl-9H-carbazol-3-yl)prop-2-en-1-one, MP: 32.4°C NMR: δ 3.84 (s, 3H,-NCH3), 7.30-7.31 (m, 1H, ArH), 7.40-7.42 (m, 4H ,ArH), 7.52 (m, 1H, ArH), 7.68 (d, 2H, J=8.64, ArH), 7.71 (d,1H, J=15.7,Olefinic H), 7.82 (d,1H, J=15.7,Olefinic H), 8.18 (m, 2H, Ar-H), 8.78 (s, 1H, ArH). IR: C-Cl 751.07, ArC-H (str) 1074.77, Ar C=C 1598.73, C=O 1670.12

Cam-I:

(2E)-3-(3-fluorophenyl)-1-(9-methyl-9H-carbazol-3-yl)prop-2-en-1-one, MP: 28.6°C NMR: 3.87 (s, 3H,-NCH3), 6.97-7.06 (m, 2H,ArH), 7.10-7.14 (m, 1H, ArH), 7.30-7.34 (m, 2H, ArH), 7.41-7.43 (m, 1H ,ArH), 7.51 (m, 2H, ArH), 7.66-7.69 (m, 2H, ArH), 7.83 -7.84 (m,1H, ArH), 8.16 (d, 1H, J=16.64, ArH), 8.22 (d, 1H, J=23.01, Olefinic H).IR: C-F 1063.21, ArC-H (str) 1074.77, Ar C=C 1598.73, C=O 1670.12

CONCLUSION:

In recent years, Carbazole alkaloids are playing important role in discovering new ant tubercular leads against non-resistant and multi-drug resistant strains of M. tuberculosis Carbazole is an important type of nitrogen-containing aromatic heterocyclic found in many natural and synthetic molecules with various pharmacological activities including antimicrobial, anticancer, anti-inflammatory, antiviral, antioxidant activities, etc Herein we report synthesis and characterization of series of Nine Novel Carbazole linked Propeonone Conjugates in excellent yields (74-89%). All the compounds were purified by Column Chromatography and later recrystaliised by Ethyl acetate/ Hexane solvent system.

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Received on 19.03.2017 Modified on 16.04.2017

Asian J. Research Chem. 2017; 10(3):271-274.

DOI: 10.5958/0974-4150.2017.00044.X