Microwave assisted synthesis and antimicrobial evaluation of schiff bases of indole-3-aldehyde

Article abstract of DOI:10.1155/2011/265329

In order to develop new antimicrobial agents, a series of Schiff bases of indole-3-aldehyde were synthesized by microwave assisted synthesis by taking DMF as solvent and evaluated for their antimicrobial activity. All the synthesized compounds were charac

Full text of DOI:10.1155/2011/265329

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(1), 305-311
http://www.e-journals.net
Microwave Assisted Synthesis and Antimicrobial
Evaluation of Schiff Bases of Indole-3-aldehyde
PRIYANKA KAMARIA*, N. KAWATHEKAR and PRERNA CHATURVEDI
Department of Pharmacy
Shri Govindram Seksaria Institute of Technology and Science
23-Park Road, Indore- 452003, (M.P.) India
kamaria.priyanka@gmail.com
Received 23 April 2010; Accepted 17 June 2010
Abstract: In order to develop new antimicrobial agents, a series of Schiff
bases of indole-3-aldehyde were synthesized by microwave assisted synthesis
by taking DMF as solvent and evaluated for their antimicrobial activity. All the
1
synthesized compounds were characterized by IR, H NMR and mass spectral
analysis. All compounds were tested against five gram positive and five gram
negative bacterial strains and one fungal strain. All compounds exhibited better
activity against gram positive strains than against gram negative strains and the
compounds were found more active against S.aureus and B.subtilis.
Keywords: Antibacterial, Antifungal, Schiff base, Indole-3-aldehyde.
Introduction
A Schiff base (or azomethine) is a functional group that contains a carbon nitrogen double
bond with the nitrogen atom connected to an aryl or alkyl group but not hydrogen1. Schiff
bases are usually synthesized from the condensation of primary amines and active carbonyl
group2. Schiff bases have been reported to possess antimicrobial properties3-7. Schiff bases
are characterized by the −N=CH− (imines) group which is important for elucidating the
mechanism of transamination and racemisation reactions in biological systems and are also
known to have biological activities such as antimicrobial8 antifungal9, antitumor10 and
herbicidal11 activity. Indole derivatives found to possess antibacterial12, anticonvulsant13 and
antihypertensive activity. These observations led to the conception that Schiff bases of
indole-3-aldehyde would possess potential antimicrobial properties. Microwave assisted
organic synthesis (MAOS) accelerate the course of many organic reactions, producing high
yields and higher selectivity, lower quantities of side products and consequently, easier
work-up and purification of the products14. In the present study a series of Schiff base of
Indole-3-aldehyde were synthesized by use of conventional microwave and characterized by

306
PRIYANKA KAMARIA et al.
IR,1H NMR and mass spectroscopy. The compounds were screened for antibacterial and
antifungal activities. The minimum inhibitory concentrations of the compounds were also
determined by serial dilution method.
Indole-3-aldehyde on condensation with different aromatic or aliphatic amine in
presence of DMF as solvent yields Schiff bases (Scheme 1).
H
N
H
N
DMF
R-NH
2
400-480W
N
R
O
Indole-3-aldehyde
Alkyl/aryl amine
Schiff base of Indole-3-aldehyde
Figure 1. Scheme for the synthesis of Schiff bases
Experimental
A mixture of 2 mmole of indole-3-aldehyde and 2 mmole of different aryl or alkyl amines
was taken and triturated in a mortar pestle. Then above mixture was transferred to a vessel
which was then kept in microwave for synthesis. 4 to 5 mL of DMF was also added to
mixture before putting it in microwave. Microwave was run at 400-480 W for different time
for different reaction mixtures. Reaction completion was monitored continuously after each
run by TLC. Then product was washed with ethanol, solvent was evaporated, dried and
recrystalized with ethanol. Structures, time in microwave assisted synthesis and % yield are
given in Table 1
Table1. Structures, time in microwave assisted synthesis and % yield of synthesized
compounds.
Compound
code
Time in microwave assisted
synthesis, min.
R
% yield
PK1
4
71.52
64.2
OH
PK2
PK3
PK4
6
C4H9
3
5
71.0
65.6
OCH3
7
68.2
Cl
PK5
PK6
NO2
12
9
64.5
62.3
HO
PK7
PK8
OH
5
62.7
H2N
Contd…

Microwave Assisted Synthesis and Antimicrobial Evaluation
307
PK9
7
72.6
NO2
NO2
10
PK10
53.3
HO
5
NO2
PK11
PK12
74.8
NH2
C
11
55.5
O
12
HN
PK13
PK14
61.6
15
F
51.7
H2N
Physicochemical and spectroscopic determination of synthesized compounds
The melting points were taken in open capillary tube and were uncorrected. Reactions were
monitored by thin layer chromatography using silica gel-GF254 as adsorbent on glass plate.
The spots were applied on silica gel plate and the plate was run in (ethyl acetate: hexane
(3:7)) in a closed chamber. The spots on the plate were detected in UV cabinet. The
differences in Rf value between starting compound and product were indicative of the
conversion of starting compound into the product.
IR spectra were recorded on FTIR-8400F model in KBr. NMR spectra were recorded on
Broker A VANCE DPX 300 instrument using TMS as internal reference and chemical shift
value are expressed in delta units. The mass spectra (ESI) were recorded on Waters
@Micromass Q-Tof Micro. It showed fragmentation pattern as m/z values. All physical and
spectral data are given in Table 2.
Table 2. Physical and spectroscopic data of synthesized compounds
Compd
code
Physical and spectral data
Yield:72.6%; Rf: 0.63{ethyl acetate: hexane (3:7)}; M.P:120-125 °C; IR(KBr cm-1)
:1570(C=C),1682.11(C=N),3042.32(C-H),1244.86(C-N),2852.41(N=CH); NMR:1H
PK1
NMR (400MHz,CDCl3) δ(ppm): 6.87-7.22(m,10H,ArH), 8.51 (s,1H; N=CH), 7.60
(s,1H,CH); (m+1)221.1
Yield:64.2%;Rf:0.82{ethyl acetate: hexane(3:7)}; M.P:160-165 °C;IR(KBr cm-1)
1502.71(C=C), 1646.39(C=N), 3090.32(C-H), 1177.41(C-N), 2856.32 (N=CH),
PK2
1
3310.52(OH); NMR: H NMR (400MHz,CDCl3) δ(ppm):6.73-7.45(m,9H,ArH),
8.63(s,1H;N=CH), 7.84(s,1H,CH), 5.30(t,1H,ArOH);(m+1) 237.1
Yield:71.0%;Rf:0.73{ethyl acetate: hexane (3:7)};M.P: 170-175 °C; IR (KBr cm-1)
1520.34(C=C),1676.34(C=N),3108.19(C-H),1243.06(C-N),2859.34(N=CH),1444.33
PK3
(CH3)bend; NMR:1H NMR(400MHz,CDCl3) δ(ppm):7.28-7.41 (m,5H,ArH), 8.61
(s,1H;N=CH),7.68(s,1H,CH),2.4(s,2H,CH2),1.7(m,5H,CH2),1.4(m,6H,CH2);(m+1)201.2
Yield:65..6%; Rf: 0.72 {ethyl acetate: hexane (3:7)}; M.P:115-120 °C; IR (KBr cm-1)
1618.17(C=C), 1682.41(C=N), 2943.37, 2903(C-H), 1244.92(C-N), 2854.56(N=CH),
PK4
1
1072.34(C-O); NMR: H NMR (400MHz, CDCl3) δ: 6.81-7.29 (m,9H,ArH), 8.53
(s,1H;N=CH),7.71(s,1H,CH),3.61(s,3H,CH3) ;(m+1) 251.1
Contd…

308
PRIYANKA KAMARIA et al.
PK5 Yield:68.2%;Rf:0.62 {ethyl acetate: hexane(3:7)};M.P:140-145 °C; IR (KBr cm-1)
1568.59(C=C), 1656.32(C=N), 3112.12(C-H), 1242.88(C-N),2857.55 (N=CH),
755.30(C-Cl); NMR:1H NMR (400MHz, CDCl3) δ:7.19-7.34(m,9H,ArH), 8.52
(s,1H;N=CH),7.60(s,1H,CH); (m+1) 255.1
PK6 Yield:64.5%;Rf: 0.79{ethyl acetate: hexane(3:7)};M.P:205-210 °C; IR (KBr cm-1)
1575.20(C=C), 1665.67(C=N), 3077.79(C-H), 1329.45(C-N), 2856.61(N=CH),
3322.97(-OH)H bonded,1498.71(R-NO2);NMR:1H NMR(400MHz,CDCl3)δ:7.71-
8.13(m,9H,ArH, 8.49(s,1H;N=CH),7.32(s,1H,CH),6.23(d,1H;ArOH); (m+1) 282.3
PK7 Yield:62.3%;Rf:0.72{ethyl acetate:hexane(3:7)};M.P:180-185 °C; IR(KBr cm-1)
1490.75(C=C), 1675.45(C=N), 3092.12(C-H), 1110.32(C-N), 2846.72(N=CH)
3220.67(-OH) H bonded; NMR:1H NMR(400MHz,CDCl3)δ:6.75-7.1(m,8H,ArH),
8.60(s,1H;N=CH),7.4(s,1H,CH),5.5(t,1H,ArOH); (m+1) 237.1
PK8 Yield:62.7%; Rf:0.80 {ethyl acetate:hexane (3:7)};M.P:155-160 °C; IR(KBr cm-1)
1530.34(C=C),1647.31(C=N),3087.42(C-H) ,1010.11(C-N),2840.42 (N=CH);
NMR: 1H NMR(400MHz,CDCl3) δ:6.52-7.01(m,9H,ArH), 8.55 (s,1H;N=CH),
7.12(s,1H,CH),4.41(s,1H,CH); (m+1) 236.3
PK9 Yield:72.6%;Rf:0.77{ethyl acetate:hexane (3:7)};M.P:145-150 °C; IR (KBr cm-1)
1545.32(C=C), 1652.32(C=N), 3085.51(C-H), 1090.17(C-N), 2842.91(N=CH),
1552.31(R-NO2); NMR:1H NMR(400MHz,CDCl3)δ:7.52-7.88(m,9H,ArH), 8.52
(s,1H;N=CH),7.41(s,1H,CH); (m+1) 266.2
PK10 Yield:53.3%; Rf: 0.65 {ethyl acetate: hexane (3:7)}; M.P:200-205 °C; IR (KBr cm-1)
1551.43(C=C), 1672.13(C=N), 3073.62(C-H), 1213.12(C-N), 2850.11 (N=CH) 3321.
51(-OH) H bonded, 1473.91(R-NO2); NMR :1H NMR (400MHz,CDCl3) δ:7.83-8.13
(m,8H,ArH), 8.51(s,1H;N=CH) ,7.32(s,1H,CH), 6.74(d,1H,ArOH) ; (m+1) 282.1
PK11 Yield:74.8%; Rf:0.70 {ethyl acetate: hexane(3:7)};M.P:130-135 °C; IR (KBr cm-1)
1530.42(C=C), 1654.56(C=N), 3092.34(C-H), 1203.56(C-N), 2848.43(N=CH),
1555.10(R-NO2); NMR:1H NMR(400MHz,CDCl3) δ:7.85-8.3(m,9H,ArH), 8.53
(s,1H;N=CH),7.6(s,1H,CH); (m+1) 266.1
PK12 Yield:55.5%;Rf:0.66 {ethyl acetate: hexane (3:7)};M.P:150-155 °C; IR (KBr cm-1)
1562.16(C=C), 1664.31(C=N), 3175.34(C-H), 1092.42(C-N), 2845.31(N=CH)
1642.51(C=O); NMR:1H NMR(400MHz,CDCl3) δ:7.25-7.50(m,5H,ArH),8.50
(s,1H;N=CH),7.71(s,1H,CH),5.71,6.12(s,2H,NH2); (m+1) 188.0
PK13 Yield:61.6 %;Rf:0.57 {ethyl acetate:hexane (3:7)};M.P:140-145 °C; IR(KBr cm-1)
1547.23(C=C), 1649.13(C=N), 3082.43(C-H), 1101.38(C-N), 2852.44(N=CH)
3392.12(R2-NH); NMR:1H NMR(400MHz,CDCl3) δ:6.70-7.17(m,8H,ArH), 8.69
(s,1H;N=CH),7.71(s,1H,CH),4.65(s,1H,ArNH); (m+1) 236.0
PK14 Yield:51.7%;Rf:0.74 {ethyl acetate: hexane(3:7)};M.P:210-215 °C; IR(KBr cm-1)
1490.34(C=C), 1674.36(C=N), 3095.65(C-H), 1215.38(C-N), 2857.13(N=CH),
1321.42(C-F); NMR:1H NMR(400MHz,CDCl3) δ:7.52-7.78(m,9H,ArH), 8.57
(s,1H; N=CH),7.21(s,1H,CH), 3.54(s,1H,ArNH); (m+1) 254.1
Antimicrobial activity
The antimicrobial activities of synthesized Schiff bases were evaluated against eleven
different strains of microorganism (Five gram positive, Five gram negative bacteria and one
fungus) using nutrient agar medium (Hi-Media Laboratories, India) and sabouraud dextrose
agar medium (Hi-Media Laboratories, India) respectively. Zone of inhibition of compounds
were determined by Cup plate method and minimum inhibitory concentration of the test
compounds were determined by two fold serial dilution technique. Dimethyl sulfoxide
(DMSO) was used as solvent for both techniques. Paper disc diffusion method for zone of

Microwave Assisted Synthesis and Antimicrobial Evaluation
309
inhibition & minimum inhibitory concentrations of the synthesized compounds were
determined by serial dilution method. Ciprofloxacin, ampicilin and fluconazole were used as
reference standards for antibacterial and antifungal activity respectively.
The lowest concentration of the test compounds showing no visible microbial
growth were considered as minimum inhibitory concentration. The observed zone of
inhibition and MIC values for bacterial and fungal strains are given in Table 3 and 4
respectively.
Table 3. Antibacterial activity of the synthesized compounds
Compd. In vitro activity-zone of inhibition in mm, (MIC in µg/mL) for gram positive strains
code
PK1
PK2
PK3
PK4
PK5
PK6
PK7
S. aureus
14(50)
15(50)
17(25)
18(25)
13(50)
12(50)
22(6.25)
12(50)
15(50)
20(12.5)
15(25)
13(50)
19(12.5)
21(6.25)
B. subtilis
19(25)
19(25)
14(50)
17(25)
24(6.25)
22(12.5)
23(6.25)
18(25)
B. cereus
18(50)
14(100)
21(25)
17(50)
18(50)
15(100)
20(25)
13(100)
19(50)
20(25)
P. fluorescence S. epidermidis
16(25)
13(50)
14(50)
13(50)
12(50)
15(25)
14(50)
11(100)
14(50)
16(25)
18(12.5)
12(50)
14(50)
13(50)
15(50)
12(100)
13(100)
16(25)
18(12.5)
16(25)
14(50)
14(50)
17(25)
10(>100)
12(100)
12(100)
16(25)
PK8
PK9
14(50)
PK10
PK11
PK12
PK13
PK14
Ciprofl-
oxacin
Amoxi-
cillin
20(12.5)
16(25)
13(50)
22(12.5)
18(25)
18(50)
16(100)
15(100)
12(>100)
15(50)
25(3.12)
33(3.12)
26(3.12)
34(3.12)
23(6.25)
25(6.25)
21(6.25)
22(6.25)
19(12.5)
20(12.5)
In vitro activity-zone of inhibition in mm (MIC in µg/mL) For gram negative strains
E. coli
18(25)
16(50)
15(50)
18(25)
22(12.5)
19(25)
21(12.5)
16(50)
15(50)
16(50)
12(100)
14(50)
15(50)
15(100)
P. aeruginosa K. pneumonae
P. vulgaris
14(100)
16(50)
11(>100)
9(>100)
12(100)
13(100)
13(100)
16(50)
17(50)
15(50)
10(>100)
15(50)
S. Typhimurium
14(100)
18(50)
PK1
PK2
PK3
PK4
PK5
PK6
PK7
PK8
19(25)
16(50)
21(25)
20(25)
17(50)
16(50)
20(25)
13(100)
15(50)
17(50)
22(25)
12(100)
15(50)
14(50)
13(100)
21(25)
13(100)
19(50)
17(50)
12(100)
17(50)
16(50)
10(>100)
9(>100)
15(50)
10(>100)
9(>100)
17(50)
11(>100)
14(100)
15(100)
17(50)
13(100)
16(50)
18(50)
15(100)
12(>100)
PK9
PK10
PK11
PK12
PK13
PK14
Ciprofl-
oxacin
20(25)
18(50)
14(100)
13(100)
11(>100)
28(3.12)
32(3.12)
24(3.12)
24(6.25)
25(6.25)
20(12.5)
23(12.5)
21(12.5)
20(12.5)
Amoxi- 3(3.12)
cillin

310
PRIYANKA KAMARIA et al.
Table 4. Antifungal activity of the synthesized compounds
Comp. Code
PK1
PK2
PK3
PK4
Zone of inhibition in mm, (MIC in µg/mL) C. albicans
15(50)
18(25)
19(25)
16(50)
PK5
PK6
20(12.5)
13(100)
18(25)
PK7
PK8
PK9
17(25)
17(25)
PK10
PK11
PK12
PK13
PK14
Fluconazole
15(50)
12(>100)
16(50)
13(100)
11(>100)
21(12.5)
Results and Discussion
We have synthesized a series of Schiff bases of indole-3-aldehyde by microwave
assisted synthesis. This protocol presented many advantages, such as good to excellent
yields, much shorter reaction time (3-15 min) and simple purification procedure. The
bioassay results revealed that most of the synthesized compounds exhibited good
antimicrobial activity. Compound (Z)-3-((1H-indol-3-yl) methyleneamino)phenol and (E)-N1-
((1H-indol-3-yl)methylene)-4-fluorobenzene-1,2-diamine showed highest antibacterial
activity with MIC of 6.25 µg/mL against S. aureus and compound (E)-N-((1H-indol-3-
yl)methylene)-4-chlorobenzenamine and (Z)-3-((1H-indol-3-yl)methyleneamino) phenol
showed highest antibacterial activity with MIC of 6.25 µg/mL against B. subtilis.
Compound (E)-N-((1H-indol-3-yl)methylene)-4-chlorobenzenamine was found to have
highest antifungal activity with MIC of 12.5 µg/mL against C. albicans.
Conclusion
The structures of synthesized compounds were confirmed by IR and NMR spectroscopy. All
compounds exhibited significant antibacterial activity but they showed moderate antifungal
activity. Further bioassay, optimization and structure-activity relationship of the title
compounds are underway.
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