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ISSN: 0976-8688
CODEN (USA): PSHIBD
156
Pelagia Research Library
T. Surendiran
Der Pharmacia Sinica, 2012, 3(1):156-159
______________________________________________________________________________
NH2NH2.H2O
R-COCH2COOC2H5
CH2Cl
1
3(a-e)
N
O
CH2 NHNH2
2
N
O
R
3a/4a CH3
N
O
N
R
4(a-e)
C6H5
p-Cl C6H5
157
Pelagia Research Library
T. Surendiran
Der Pharmacia Sinica, 2012, 3(1):156-159
______________________________________________________________________________
(4c)N-acetyl-(3-phenyl-1H-pyrazole-(4H)-5-on)-yl-1,2,3,4-tetrahydrocarbazole
IR (KBr):1625, 1680, 1630 Cm-1; 1HNMR : 1.84-1.96(m,4H,2CH2), 2.45(d,2H,CH2), 2.72-2.79(m,4H,2CH2), 4.42
(s,2H,CH2-N) 4.48(s,2H,CH2-N) 5.56 (s,1H, NH),6.98-7.20(m,9H,ArH) Melting point: 145oC; Yield 55% ;MF C22
H19 N3O2:(m/z) 357.08;Elemental Analysis Calcd(Found) :C : 73.93(73.95);H: 5.36(5.38);N: 11.76 (11.78).
(4d) N-acetyl-(3-(p-methyl phenyl) -1H-pyrazole-(4H)-5-on)-yl-1,2,3,4- tetrahydrocarbazole
IR (KBr):1615, 1630, 1656 Cm-1; 1HNMR : 1.81-1.92(m,4H,2CH2), 2.32 (s, 3H, CH3), 2.43(d,2H,CH2), 2.732.78(m,4H,2CH2), 4.40 (s,2H,CH2-N) 4.42(s,2H,CH2-N) 5.50 (s,1H, NH),6.92-7.40(m,8H,ArH) . Melting
point:
156oC; Yield 65% Molecular Formula:C23 H21 N3O2 (m/z) :355.21; Elemental Analysis: Calcd.(Found) :C :
77.72(77.74);H: 5.96(5.98);N: 11.82 (11.84).
(4e) N-acetyl-(3-(p-chlorophenyl)-1H-pyrazole-(4H)-5-on)-yl-1,2,3,4-tetrahydrocarbazole
IR (KBr):1614, 1632, 1666 Cm-1; 1HNMR : 1.84-1.96(m,4H, 2CH2), 2.34(d, 2H, CH2), 2.70-2.76(m,4H,2CH2),
4.44 (s,2H,CH2-N) 4.34(s,2H,CH2-N) , 5.53 (s,1H, NH),6.90-7.44(m,8H,ArH):Melting point: 156oC; Yield 60%
Molecular Formula:C18 H19 N3O2 (m/z) : 391.20;Elemental Analysis: Calcd.(Found) : C : 67.43(67.45);H:
4.63(4.65);N: 10.76 (10.78).
2.4 Antimicrobial studies
Newly synthesized compounds 3(a-e) were screened for their in vitro antibacterial activity against Bacillus cereus,
Bacillus subtilis, Streptococci mutans, and Micrococcus luteus, at concentration of 25g using ciprofloxacin as
standard and antifungal activity against Aspergillus niger, Candida albicans Altenaria macrospora and Fusarium
oxysporum at concentration of 25 g using ketoconazole as standard . DMF was used as solvent control, nutrient
agar was used as culture medium and method employed was cup [11] plate method. The zones of inhibition formed
were measured in mm and are shown in Tables I and II respectively to antibacterial and antifungal activities
Table -I Antibacterial activity of compounds 3a-e (zone inhibition in mm)
Compound B.cereus B.subtilis S.aureus M.luteus
4a
18
18
17
19
4b
27
29
28
25
4c
23
22
24
25
4d
23
26
21
24
4e
25
27
24
26
DMF-negative control; Reference Standard ciprofloxacin
Table -II Antifungal activity of compounds 3(a-e) (zone inhibition in mm)
Compound A.nigar C.albicans F.oxysporum A.macrospora
4a
17
19
18
15
4b
27
26
28
26
4c
19
20
18
17
4d
24
23
21
23
4e
26
24
28
26
DMF-negative control; Reference Standard Ketoconazole
RESULTS AND DISCUSSION
The hydrazinolysis of compound 1[12] with hydrazine hydrate afforded N-(hydrazinoacetyl)-1,2,3,4tetrahydrocarbazole 2. The 1HNMR spectrum of hydrazide 2, showed a singlet for N-H at 3.1 ppm and singlet for
NH2 2.90 ppm. Its IR spectrum showed a band between 3094and 3316cm-1.The disappearance of the hydrazide
peaks and appearances of new absorption peaks at 1620cm-1 and 1628 cm-1 for carbonyl stretching for CO-CH2-C
and CO-CH2-N respectively has confirmed cyclization of the hydrazide to compound N-acetyl- (3-methyl-1Hpyrazole- (4H)-5-on)-yl-1,2,3,4-tetrahydrocarbazole 4a.
158
Pelagia Research Library
T. Surendiran
Der Pharmacia Sinica, 2012, 3(1):156-159
______________________________________________________________________________
In 1HNMR spectrum, appearance a new doublet at 2.40 ppm for methylene protons confirmed the hydrazide has
been converted to pyrazolinone. Further, a sharp singlet peak appeared at 3.0 indicates the presence of methyl
group in pyrazolinone .The remaining peaks, a multiplet at 7.08 integrating for four aromatic protons and a singlet
at 4.42 for methylene protons as in N-(hydrazinoacetyl)-1,2,3,4-tetrahydro carbazole confirms the structure of the
compound. The mass spectrum showed the molecular ion peak at 308.50(40%) and the major fragmentations are
appeared at 278.72(22%), 227.92(15%), 166.82 (35%) 148.80(80%) and 128.99(24%).
Antibacterial activities of all the newly prepared compounds against four bacteria are presented in Table I .The
antibacterial activity of compounds 4b and 4e are respectively having ethyl and p-chloro phenyl groups in
heterocyclic moieties found to be excellent. The compounds 4a and 4d are having methyl and p-methyl phenyl
group exhibited better activity than compounds 4a. (Shown in Table I)
Antifungal activities of all the newly prepared compounds against fungi are presented in Table I. The antifungal
activity of compounds 4b and 4e are excellent activity towards Fusarium oxysporum and Altenaria macrospore
among the four organism. The compounds 4c and 4d are having moderate activity where as 4a having considerable
activities for the tested organisms (Shown in Table II)
Acknowledgement
The authors are grateful to Dr.Ceeal Analytical Lab, Thorappakkam, Chennai for providing antimicrobial studies.
The authors are also grateful to SAIF, IIT, Chennai, providing spectral data for the derived compounds.
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