Synthetic studies of Alkoxy isoindole-1,3-diones tetra-azabenzo[f]azulenes and their Antibacterial activity

CODEN ECJHAO http://www.e-journals.net E-Journal of Chemistry Vol. 3, No.1, pp 28-34, January 2006 Synthetic studies of Alkoxy isoindole-1,3-diones tetraazabenzo[f]azulenes and their Antibacterial activity M. AHMED, R. SHARMA, D. P. NAGDA, V. K. SALVI and G. L. TALESARA* Synthetic Organic Chemistry Research Laboratory Department of Chemistry M. L. Sukhadia University Udaipur (Raj)-313 001 (India) E-mail: , Received 2 October 2005; Accepted 23 January 2006 Abstract: 3-Methylpyrazol-5-one 3 reacts with substituted benzaldehydes 4a-d in the presence of anhydrous sodium acetate to produce the corresponding 4arylidene-5-methyl-2,4-dihydro-pyrazol-3-ones 5a-d and the condensation of 5a-d with 2-bromoalkoxy-1H-isoindole-1, 3-(2H)-diones 2a-c furnished corresponding 2-[2-(4-arylidene-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)alkoxy]-isoindole-1,3diones 6a-l, which on cyclisation with o-phenylendiamine give titled compounds 7a-l. All the synthesized compounds have been characterized by elemental analysis and spectral data and screened for their antibacterial properties against various bacterial strains in order to obtain chemotherapeutic properties. Key words:. Synthetic studies, antibacterial activity Introduction A great deal of synthesis work has been done in last few years on various compounds having a condensed diazepine nucleus, especially benzodiazepin have attracted the attention of several chemist and biologists because of their valuable therapeutic properties like tranquillizer1-3, neuroleptic agents4, antineoplastic5,6, HIV-1 RT inhibitors7,8 antileukemic9 and antifungal10 etc. It is interesting to note that pyrazoles are also reported as well known pharmacophores11-14. As a part of our studies aimed to synthesis of various heterocyclic imidoxy derivatives and in continuation to our work15-18 it seems interesting to integrate structural features from different biological active compounds in a single molecule. Consequently there have been many efforts for designing of novel, hybrid molecules possessing significant bioactivity. In the present work, we report the synthetic efforts to 29 G. L. TALESARA et al synthesize alkoxy isoindole-1,3-dionestetra-azabenzo[f]azulenes containing benzodiazepine, pyrazole and imidoxy moieties. Experimental Melting points were determined in open capillary tubes and are uncorrected. The time required for completion of the reaction was monitored by TLC using Silica gel-G plates and spots were exposed in iodine chamber. IR spectra were recorded on a Perkin Elmer 1800 (FTIR) spectrometer 1H NMR spectra (CDCl3) were taken on a DRX-300 spectrometer (300 MHz) using TMS as internal standard and chemical shifts are expressed in δ ppm. Mass spectra were taken on a jeol SX-102/DA-6000 spectrometer. 2-Hydroxy-1H-isoindole-1,3dione20 1, 2-Bromoalkoxy-1H-isoindole-1,3-(2H)-diones21 2a-c and 3-methylpyrazol-5-one22 3 were prepared by the reported methods. Synthesis of 4-(4'-methoxybenzylidene)-5-methyl-2,4-dihydro-pyrazol-3-one 5a. A mixture of 3-methylpyrazol-5-one 3 (0.98 g, 0.01 mole), anisaldehyde 4a(1.12 ml, 0.01 mole) and anhydrous sodium acetate (0.82 g, 0.01 mole) were suspended in acetic acid (30 ml) and refluxed for 10 hours. The reaction mixture was filtered and the filtrate was poured on crushed ice. The solid obtained, was crystallised from ethanol. Compounds 5b-d were also synthesized by the similar method using appropriate reactants with required change in reflux time. 5a: (c.f. Table 2); IR (KBr)(cm-1): 3435 (N-H), 3076 (Ar-H), 2964 (C-H, CH3), 1690(C=O), 1602 (C=N); 1H NMR (CDCl3): 8.2 (s, 1H, N-H), 7.4-7.0 (m, 4H, Ar-H), 6.1(s, 1H, C=CH), 3.7 (s, 3H, OCH3), 1.7 (s, 3H, CH3). 5b; IR (KBr) (cm-1): 3412 (N-H), 3080 (Ar-H), 2952 (C-H, CH3), 1718 (C=O), 1612 (C=N), 728 (Ar-Cl); 1H NMR (CDCl3): 8.0 (s, 1H, N-H), 7.3-6.9 (m, 4H, Ar-H), 6.2 (s, 1H, C=CH), 1.8 (s, 3H, CH3). 5c; IR (KBr) (cm-1): 3396 (NH), 3062 (Ar-H), 2946 (C-H, CH3), 1705 (C=O), 1612 (C=N); 1H NMR (CDCl3): 8.1 (s, 1H, N-H), 7.4-7.1 (m, 5H, Ar-H), 6.3 (s, 1H, C=CH), 1.8 (s, 3H, CH3). 5d; IR (KBr) (cm-1): 3410 (N-H), 3070 (Ar-H), 2950 (C-H, CH3), 1710 (C=O), 1626 (C=N); 1H NMR (CDCl3): 8.1 (s, 1H, N-H), 7.6-7.2 (m, 4H, Ar-H), 6.2 (s, 1H, C=CH), 2.0 (s, 3H, CH3), 1.7 (s, 3H, pyrozole-CH3). Synthesis of 2-[2-{4-(4'-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-pyrazol1-yl} ethoxy]-isoindol-1,3-dione 6a. A mixture of compound 5a (2.16 g, 0.01 mole), with 2-bromoethoxy-1H-isoindole-1, 3(2H)-dione 2a (2.70 g, 0.01 mole) and pyridine (2 ml) were refluxed in absolute alcohol (30 ml) for 11 hrs. Excess of the solvent from the filtrate was removed under reduced pressure. On cooling, the solid separated was crystallized from ethanol. Compounds 6b-l were also synthesized by the similar method using appropriate reactants and minor modification in reaction conditions. 6a: (c.f. Table 2); IR (KBr) (cm-1): 3072 (Ar-H), 2932 (C-H, CH3), 2837 (C-H, CH2), 1755 (C=O, CO-N-CO), 1722 (C=O, pyrazole ring), 1603 (C=N), 1270 (C-N); 1H NMR (CDCl3): 7.6-7.0 (m, 8H, Ar-H) 6.7, (s, 1H, C=CH), 3.6 (s, 3H, OCH3), 3.4 (t, 2H, OCH2 CH2 N), 2.8 (t, 2H, OCH2 CH2 N), 1.9 (s, 3H, CH3). 6c: (c.f. Table 2); IR (KBr) (cm-1): 3068 (Ar-H), 2946 (C-H, CH3), 2848 (C-H, CH2), 1776 (CO-N-CO), 1698 (C=O, pyrazole ring), 1620 (C=N), 1280 (C-N); 1H NMR (CDCl3): 7.7-7.2 (m, 9H, Ar-H), 6.8 (s, 1H, C=CH), 3.4 (t, 2H, OCH2CH2 N), 2.8 (t, 2H, OCH2 CH2 N), 1.9 (s, 3H, CH3). 6f: (c.f. Table 2); IR (KBr) (cm-1): 3066 (Ar-H), 2940 (C-H, CH3), 2842 (C-H, CH2), 1770 (CO-N-CO), 1705 (C=O, pyrazole ring), 1616 (C=N), 1283 (C-N), 746 (Ar-Cl); 1H NMR (CDCl3): 7.5-7.1 (m, 8H, Synthetic and their antibacterial activity studies 30 Ar-H), 6.6 (s, 1H, C=CH), 3.5 (t, 2H, OCH2CH2CH2N), 2.8 (t, 2H, OCH2CH2CH2N), 2.5 (quint, 2H, OCH2CH2CH2N), 1.8 (s, 3H, CH3). 6l: (c.f. Table 2); IR (KBr) (cm-1): 3076 (Ar-H), 2950 (C-H, CH3), 2838 (C-H, CH2), 1750 (CO-N-CO), 1700 (C=O pyrazole ring), 1602 (C=N), 1286 (C-N); 1H NMR δ (CDCl3): 7.3-6.8 (m, 8H, Ar-H), 6.7 (s, 1H, C=CHAr), 3.4 (t, 2H, OCH2CH2CH2CH2N), 2.8 (t, 2H, OCH2CH2CH2CH2N), 2.2 (s, 3H, CH3), 1.8 (s, 3H, Pyrazole CH3). Synthesis of 2-[2-{10-(4'-methoxyphenyl)-1-methyl-10,10a-dihydro-9H-2,3,4,9tetra-azabenzo [f] azulen-3-yl}ethoxy]-isoindol-1,3-dione 7a. Compound 6a (4.05 g, 0.01 mole) was dissolved in 80 ml hot xylene in round bottomed flask and o-phenylenediamine (1.08 g, 0.01 mole) was also dissolved in 20 ml boiling xylene. Now the boiling solution of o-phenylenediamine was added in small installments to the solution of 6a and refluxed for 8-10 h. During the reaction water formed was separated by Dean-stark apparatus. Excess of solvent was then removed under reduced pressure. The residue was titurated with light petroleum ether and benzene (9:1) to give final product. It was filtered and recrystallized from light peterolium benzene. Compounds 7b-l were also synthesized by the similar method using appropriate reactants. 7a: (c.f. Table 2); IR (KBr) (cm-1): 3432 (N-H), 3060 (Ar-H) (...truncated)