Microwave Synthesis , Characterization and Antimicrobial activity of some Chromene derivatives

In the present study the synthesis of Chromene derivatives 7-ethyl-2, 3, 4, 4a-tetrahydro1H-xanthen-1-one (3a), 7-bromo-2, 3, and 4, 4a-tetrahydro-1 H-xanthen-1-one (3b), 5-ethoxy-2, 3, and 4, 4a-tetrahydro-1 H-xanthen-1-one (3c),7-ethyl-3, 3a-dihydrocyclopenta[b]Chromen1(2H)-one (4a), 7-bromo-3, 3a-dihydrocyclopenta[b]Chromen-1(2H)-one (4b),and 5-ethoxy -3, 3a-dihydrocyclopenta[b]Chromen-1(2H)-one (4c) have been reported by the reaction of substituted Salicylaldehyde with 2-cyclopenten-1-one/2-cyclohexen-1-one in the presence of ammonium acetate with ethanol using microwave-irradiation. The Microwave synthesized complexes have been categorized via IR, 1H-NMR, 13C-NMR, Mass Spectroscopy then elemental analysis. In this Microwave irradiation method contains two scheme, in the Scheme 2 gives high yield compare to Scheme 1.In the antibacterial and anti-fungal study the compounds 3b, 4a shows good and 4b shows very good activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus and 3b, 3c shows good activity against Aspergillus Niger, Penicillium species and Candida albicans, compare to others. Short reaction time, environment friendly products, high economical, excellent yield and good microbial activity are the highest benefits of this technique which create high commercial value than the other methods.


INTRODUCTION
Eco-friendly synthetic procedure is a novel and promptly developing methods of medicinal chemistry.It's very fast growing importance is used for medicinal chemistry research fields because these methods are constructed to avoid the chemical waste and save the time.Microwave irradiation [1][2][3] method is the greatest changes for traditional chemical synthetic root.Through applying the eco-friendly synthetic technique, we can eliminate the use of poisonous thinners, hazardous producing substances and also the elimination of by-product.Gedye with Giguere (1986) stated for the paramount period that a natural organic synthesis might be directed precisely quickly under microwave synthesis methods.In the medicinal chemistry and natural products field 2H-Chromenes (2H-1-Benzopyrans) are acting as an important intermediate [4][5] for many organic synthesis.Generally some Chromene containing compound used for the intermediates of positive logically arising product, such as Miroestrol compound.Coumarins compounds act as a very good antioxidant 6 and equally fluorescent methods, pointers for custom in evaluating, stabilizers, besides with medicinal usage for their, diuretic, anticoagulant, anti HIV 7 , antitumor, anti-inflammatory [8][9][10] , anticanser 11 , anti-Alzheimer's [12][13] , central nervous system activity 14 anti-leukemic, anti-bacterial [15][16][17][18][19][20][21][22][23][24][25] , anti-malarial events 26 , emetic 27 .Furthermore, they can be working as grease, paints, colors and used as possible eco-friendly agrochemicals.It has been reported [28][29][30][31][32] that poly functional vinylic compounds can be prepared by using Ammonium acetate substrates.The structures of microwave synthesized Chromene derivatives assumed from their elemental analysis (C, H, O, N, and Br) and IR, 1 H, 13 C -NMR, Mass spectra and tested the antimicrobial activity.In our knowledge this tecnique is the best methods for microwave synthesis and microbial activity of Chromene derivatives because this is eco-friendly simple method, good yield, short time and more economical.

ExpERIMENTAL
Use the open capillary tube to find out the compound melting points.FT-IR spectra data (KBR) were taken on Perkin-Elmer1300 FT IR spectrometer and Bruker WM-400 instruments (FT NMR400 MHz) recorded 1 H NMR & 13 C NMR (Internal standard-TMS), GC-MS spectra were recorded on GC-Mass spectrometer instruments.Total products presented suitable small analytical report.Cleanliness of the product was tested by thin layer chromatography methods.

Synthesis of 7-Bromo-2, 3, and 4, 4a-tetrahydro-1H -xanthen-1-one (3b)
With a mixture of 5 mm 5-Bromo-2hydroxybenzaldehyde in ethanol (few ml) and 20% per mole of ammonium acetate followed by of 2-Cyclohexen-1-one (10 mm) added and the constant stirring continued on Microwave irradiation for 5 minute.Then the reaction compound was converted into an acid medium with a few ml of concentrated HCl and the bottom level was detached, wash the aqueous level with DCM.The compound deposit was dehydrated and, after the distillation process, providing the Chromene compound 7-bromo-2, 3, and 4, 4a-tetrahydro-1 H-xanthen-1-one (3b)) and in good yield (Table 1, Scheme 1).

Scheme 2 Synthesis of 7-Ethyl-3, 3a-dihydrocyclopenta[b] Chromen-1(2H)-one (4a)
With a mixture of 5 mm 5-ethyl-2-hydroxy benzaldehyde in ethanol (few ml) and 20 mole% of Ammonium acetate followed by of 2-cyclopenten-1-one (10 mm) added and the constant stirring continued on Microwave irradiation for 5 minute.Then the compound was converted into an acid medium with a few ml of concentrated HCl and the bottom level was detached, wash the aqueous level with DCM.The organic compound deposit was dehydrated and, after the distillation process, providing the Chromene compound 7-Ethyl-3, 3a-dihydrocyclopenta[b]Chromen-1(2H)-one (4a) and in good yield.(

7-bromo-3, 3a-dihydrocyclopenta[b]Chromen-1(2H)-one (4b)
With a mixture of 5 mm 5-bromo-2hydroxybenzaldehyde in ethanol (few ml) and 20% per mole of Ammonium acetate followed by of 2-cyclopenten-1-one (10 Mm) added and the constant stirring continued on Microwave irradiation for 5 minute.Then the compound was converted into an acid medium with a few ml of concentrated HCl and the bottom level was detached, wash the aqueous level with DCM.The organic compound deposit was dehydrated and after the distillation process, providing the Chromene compound 7-Bromo-3, 3a-dihydrocyclopenta[b]Chromen-1(2H)one (4b) and in good yield.(Table 2, Scheme 2).

RESULTS AND DISCUSSION
The green synthesis of all sequences of the final product was prepared by the reaction substituted salicylaldehyde and ammonium acetate followed by of 2-cyclohexen-1-one added in the presence of Microwave irradiation.Formation of 3a-3c was established by the occurrence of C-O-C extending peaks at 1279,1266&1290, lmax, cm -1 and aromatic C=O group stretching peaks at 1647,1702&1688, lmax, cm -1 in IR and aromatic group singlet at 7.75,8.29 & 7.98, lmax, cm -1 for the xanthene cyclic group in 1 HNMR spectra. 1 H-NMR spectrum valued showed a fine triplet at δ 5.03,5.&5.18 due to a xanthene group of their structure were found over spectral values and physical data (Table 1).FT-IR and In other methods, the reaction of Substituted Salicylaldehyde and ammonium acetate followed by of 2-Cyclopenten-1-one added in the presence of Microwave irradiation.Formation of 4a, 4b and 4c was established by the occurrence of C-O-C group stretching peaks at 1223, 1275 & 1250, lmax, cm -1 and C=O is stretching peaks at 1667, 1667.41 & 1710, lmax, cm -1 in FT-IR and aromatic group singlet at 7.751, 8.06 & 7.55 cm -1 for the Chromene cyclic group in 1 HNMR spectra.

Antibacterial activity
Novel synthesized Chromene derivatives are selected for their anti-bacterial behavior in vitro beside the species of Escherichia coli (Gram -ve, micro-organism), Pseudomonas aeruginosa (Gram -ve, micro-organism) and Staphylococcus aureus (Gram +ve, micro-organism) by agar well (disk) diffusion techniques.Ciprofloxacin is used as a standard drug and the outcomes are

Anti-fungal activity
Novel green synthesized Chromene compounds are selected for their antifungal behavior in vitro beside the micro-organism of Penicillium Commercial Amphotericin-B is used as a standard and the outcomes are displayed in Table 4 and Fig. 2. In the anti-fungal study the compounds 3b and 3c shows very good activity against Aspergillus Niger, Penicillium species, Candida albicans and, compare to others.

CONCLUSIONS
Microwave assisted synthesis of Substituted Salicylaldehyde with 2-cyclopenten-1-/2-cyclohexen-1-one in the presence of ammonium acetate with ethanol gives a good yield of some novel Chromene compounds (3a-3c and 4a-4c).In this synthetic Microwave irradiation method the compound 4a-4c (Table 1) gives high yield.Total compounds are lively against all the verified bacterial and fungal strains.Compound 3a-3c and 4a-4c are medium or more active against antibacterial and fungal strains for standard drug and antibacterial activity.In the antibacterial and anti-fungal study the compounds 3b, 4a shows good and 4b shows very good activity against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli and 3b, 3c shows very good activity against Aspergillus Niger, Penicillium species and Candida albicans, compare to others.This research work has high economic, because used available and simple catalyst, simple reaction methods, need less time and get ecofriendly nature.opportunity to complete the research and for their constant encouragement to write the article in good form and Dr. G. Sarawathi, HOD of chemistry.
Government Engineering College Bargur, Tamilnadu, India for their encouragement and providing necessary research facilities.