Synthesis, Structure and Spectral Charectarization of Friedal Craft N-Benzylation of Isatin and Their Novel Schiff’s Bases

 

RA Hajare*1, RM Gaurkhede1,  PP Chinchole1, AV Chandewar1, AS Wandhare1 and SS Karki2

*P.W. College of Pharmacy, Dhamangaon Road, Yavatmal. 445001 (M.S.)

1K.L.E. College of Pharmacy, Rajaji Nagar, Bangalore - 560010.

*Corresponding Author E-mail: rahulhajare@rediffmail.com

 

 

ABSTRACT

Isatin (1H-indole-2, 3-Dione) is synthetically versatile molecule. Erdman and Laurent first obtained it in 1841 as a product from the oxidation of indigo by nitric acid and chromic acid. Isatin (Indole 2’3 dione), its 5-halo derivatives were reacted to form the Schiff’s bases,Mannich bases and Friedal Craft Alkylation’s to form C-C, C-N, C=N bonds. From the spectral studies it reveals that the isatin were undergoes reaction at C-3 and N-1 position. The structures of the synthesized derivatives were characterized from 1 H-NMR, IR spectral data and elemental analysis. The most of the compound synthesized were shown to possess biological activity.

 

KEYWORDS:  Isatin, Schiff’s Base, N-Benzylation, Dimethyl formamide.

 

 

INTRODUCTION:

Isatin is an endogenous compound isolated in1988 and reported to possess a wide range of activity. Isatin is the biologically active chemical produced by an Alteromones spstrain inhibiting the surface of embryo of the cardiean shrimp Palaemon macrodectylus, which protects them from the pathogenic fungus Lagenidium allinectes.1,2 The literature study reveals that the Schiff’s bases, Mannich bases and the compound obtained on Friedal Craft alkylation’s are show a wide range of activity .They have reported to possess anti-bacterial, anti-fungal,cytotoxic and anti-HIV activity.3,4,5 In the view of this fact the various derivatives of the isatin were synthesized for the spectral analysis.

 

MATERIAL AND METHODS:

All the chemicals were of laboratory grade and were purified by the established method. The melting points were determined by open capillary tube method and are uncorrected. The purity and homogeneity of the synthesized compound was ascertained by T.L.C. on glass plate using silica gel G as adsorbent and solvent system benzene: ethanol (9:1). The spot were visualized by iodine vapor. The FT-IR spectra were recorded using KBr disc on Shimadzu-8101A infrared spectrometer, 1H-NMR spectra on CDCL3 (Bruckrs) and UV Spectroscopy (Thermo Electronic Corporation).

 

GENERAL PROCEDURE:

Methods of preparation of 5-substituted N-benzyl isatin derivatives: 6

In RBF take equimolecular quantity of isatin and benzyl chloride. To this mixture add 20 ml of dimethyl formamide and pot. Carbonate. After gently shaking the mixture refluxed for 2hrs. Cool the mixture and pour into the 100 ml of ice cold water. The resultant orange colour precipitate is collected and washes with water. Dried and recrystalized from ethanol. M.P. is 1200­­­­C-1300­­­­C

 

Methods of preparation of Schiff’s bases of 5-substituted N-benzyl isatin derivatives:

Equimolecular quantity of N-benzyl derivatives and amines were added into 20ml of absolute ethanol in 250 ml of round bottom flask. To this mixture add few drops of glacial acetic acid. The reaction mixture was refluxed for 2-3 hour and checked for completion. After completion of reaction placed the mixture for 24 hour, filtered and recrystalized from ethanol.

 

The all synthesized compound were analyzed by FT-IR spectra using KBr disc on SHIMADZU-8101A infrared spectrometer, 1H-NMR spectra on CDCL3 (Bruckrs) and UV Spectroscopy (Thermo Electronic Corporation).

 

The reproducibility of the developed method was ascertained by considering the physical properties of the synthesized compound. 

 

 

SCHEME -I

 

 

R1 = H, Cl, F, NO2

 

SCHEME -II

 

       


N-benzyl 3-[(phenylimino)-hydrazono]-1,3-dihydro-indole-2one (P-01)

Yield 70%, m.p.2600C, Rf value 0.6, I.R (cm-1) C=N1612, C=O1662, C-H 785, C-NH 3088; 1H-NMR (1H) =N-NH d 12.82, (4-H) d 7.6, (2 Ar-H) N-CH2 d 6.6 , UV(λmax,nm) 247,365.

 

N-benzyl 3-[(2, 4-dinitrophenylimino)-hydrazono]-1, 3-dihydro-indole-2-one (P-02)

Yield 70%, m.p. >3000C Rf value 0.53, I.R (cm-1)C-NO­2 1315,C=N1608, C=O1722, C-H 785,C-NH 3325; 1H-NMR (1H) =N-NH d 12.82,  (4-H ) d 7.6, (2 Ar-H) N-CH2 d 6.6 , UV(λmax,nm) 230, 371.

 

3-[(phenylimino)-hydrazono]-1,3- dihydro-indole-2-one (P-03)        

Yield 76%,m.p.>2200C,Rf 0.46value, I.R (cm-1) C=N1618, C=O1686, C-H 748,C-NH 3161, 1H-NMR (1H) =N-NH d 12.7,  (4-H) d 7.8, (4 Ar-H) d  7.3, UV(λmax,nm) 258, 381.

 

3-[(2,4-dinitro-phenylimino)-hydrazono]-1,3- dihydro-indole-2-one (P-04)

Yield  80%,m.p. >2900C, Rf value0.5, I.R. (cm-1) C-NO2 1313, C=N 1612, C=O1730, C-H 740, C-NH 3316 , 1H-NMR (1H) =N-NH d 12.15,  (4-H) d 8.5, (2 Ar-H) d  7.4 , UV(λmax,nm) 254,380.

 

N-benzyl 3-[(phenylimino)-hydrazono]-5-Chloro-1,3-dihydro-indole-2-one (P-05)

Yield 40%, m.p. >3000C  Rf value0.7, I.R. (cm-1)  C-Cl 640,C=N1676, C=O 1718, C-H 735 , 1H-NMR (1H) =N-NH d 12.8,  (3-H) d 7.6 , (4 Ar-H) d  7.3, (2H) N-CH2 d  6.6 , UV(λmax,nm) 248,259

 

3-[(phenylimino)-hydrazono]-5chloro-1,3-dihydro-indole-2-one (P-06)

Yield 70%, m.p. >3000C Rf value 0.53, I.R (cm-1) C-Cl­ 633,C=N1618, C=O1678, C-H 754,C-NH 3438, 1H-NMR (1H) =N-NH d 11.14,  (3-H) d 7.5 , (4 Ar-H) d  7.3, UV(λmax,nm) 248,259.

 

3-[(2,4-dinitro-phenylimino)-hydrazono]-5Chloro-1,3-dihydro-indole-2-one (P-07)

Yield 80%, m.p. >3500C Rf value 0.52, I.R (cm-1)  C-Cl­ 493,C=N1613, C=O1733, C-H 721,C-NH 3373 , 1H-NMR (1H) =N-NH d 9.4,  (3-H) d 8.3, (3 Ar-H) d  7.3, UV(λmax,nm) 257,370.

 

3-[(phenylimino)-hydrazono]-5 Fluro-1,3-dihydro-indole-2-one(P-08)

Yield 45%, m.p. 2700C Rf value 0.9, I.R (cm-1) C-F­1041 ,C=N 1599, C=O1678, C-H 779,C-NH 3165,  1H-NMR (1H) =N-NH d 12.7,  (3-H) d 7.6, (4Ar-H) d  7.3, UV(λmax,nm) 249,385.

 

3-[(2,4-dinitro-phenylimino)-hydrazono]-5 Fluro-1,3-dihydro-indole-2one (P-09)

Yield 50%, m.p. >3500C Rf value 0.51, I.R(cm-1)  C-F­ 1007, C-NO­2 493,C=N1616, C=O1741, C-H 740, C-NH 3306,  1H-NMR (1H) =N-NH d 12.7,  (3-H) d 7.6, (2Ar-H) d  7.3, UV(λmax,nm) 252,360.

 

3-[(phenylimino)-hydrazono]-5 Nitro-1,3-dihydro-indole-2-one (P-10)

Yield 72%, m.p. 3000C Rf value 0.9, I.R(cm-1) C-NO­2 1315, C=N 1593, C=O1682, C-H 758,C-NH 3109,   1H-NMR (1H) =N-NH d 12.7,  (3-H) d 7.6, (2 Ar-H) d  7.3, UV(λmax,nm) 262,365.

 

3-[(2,4-dinitro-phenylimino)-hydrazono]-5 Nitro-1,3-dihydro-indole-2-one (P-11)

Yield 80%, m.p. >3500C Rf value 0.5, I.R (cm-1) C-NO­2 1336,C=N1616, C=O1722, C-H 787,C-NH 3400, 1H-NMR (1H) =N-NH d 9.4,  (3-H) d 8.5, (3 ArH) d  7.5, UV(λmax,nm) 271,368.          

 

RESULT AND DISCUSION:

From the comparative study of the results obtained from FT-IR, 1H-NMR and UV Spectral data, all synthesized compound on the basis of schiff’s base and Friedal craft N-benzylation, were found to be satisfactorily.

 

AKNOWLEDGEMENT:

We are thankful to N.M.R Research center, Indian Institute of Sciences, Bangalore-560012 who provide us facility for N.M.R. analysis. Thanks are Head, Department of Pharmaceutical sciences, UDCT, Nagpur, for providing facilities for I.R. analysis.

 

REFFERANCE:

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2)       Verma M, Pandeya S. N, Singh K. N and Stables J. P. Anticonvulsant activity of Schiff bases of isatin derivatives. Acta. Parma. (2004); 54:49-56

3)       Elizabeth I.C, Gut H. J, Rosenthal  P. J, McKerrowb J. H  and.Chibale K. Synthesis and Evaluation of Isatins and Thiosemicarbazone Derivatives against Cruzain, Falcipain-2 and Rhodesain. Bioorganic and Medicinal Chemistry Letters. (2003); 13: 3527–3530

4)       Chiyanzu I, Clarkson C, Smith P.J, Lehman J , Gut J , Rosenthalc P. J  and. Chibalea K. Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorganic and Medicinal Chemistry. (2005); 13:3249–3261

5)       Terzioğlu N, Karalı N, Gürsoy A , Pannecouque C, Leysen P, Paeshuyse Jan,. Neyts J, and De Clercq E. Synthesis and primary antiviral activity evaluation of 3- hydrazono-5-nitro-2-indolinone derivatives. ARKIVOC. 2006; (i): 109-118

6)       Jarrahpour A, Khalili D, De Clercq E , Salmi C, and Brunel J. Synthesis, Antibacterial, Antifungal and Antiviral Activity Evaluation of Some New bis-Schiff Bases of Isatin and Their Derivatives. Molecules. 2007; 12: 1720-1730

7)       Singh G.S and Luntha P. Synthesis and antimicrobial activity of new 1-alkyl/cyclohexyl-3, 3-diaryl-10-methylspiro [azetidine-2, 30-indoline]-20, 4-diones. European Journal of Medicinal Chemistry. (2008); xx: 1e5.

8)       Güzel  Ö, Terzioğlu N, Çapan, G and Salman A.  Synthesis and biological evaluation of new 5-methyl-N-(3-oxo-1-thia-4-azaspiro[4.5]-dec-4-yl)-3-phenyl-1H-indole-2-carboxamide derivatives. ARKIVOC. 2006; (xii): 98-110 ISSN 1424.

9)       Ramachary D.B, Reddy G.B and Mondal Rumpa. A new organocatalyst for friedel craft alkylation of 2-napthol with isatin: application of an organo-click strategy for cascade synthesis of highly functionalized molecules. Tetrahedron letters. (2007); 48: 7618-7623. 

10)    Sridhar S.K, Pandeya S and Stables J.Anticonvulsant activity of hydrazones,Sciff’s and mannich bases of isatin derivatives. Eur.j.Pharm.Sci. (2002); 16:129-132.

11)    Pandeya S, Sriram D, Nath G and De Clercq E.  Synthesis, antibacterial antifungal and anti-HIV activities of Schiff and Mannich bases of isatin derivatives with 3-amino-2-methyl-mercaptoquinazoline-4(3H)-one. Pharmaceutica Acta Helvetia. (1999); 74: 11-17

 

 

 

 

Received on  10.06.2009        Modified on 28.06.2009

Accepted on 14.07.2009        © AJRC All right reserved

Asian J. Research Chem.  2(3): July-Sept., 2009, page 289-291