Indian Journal of Chemistry Vol. 39B, June 2000, pp. 440 - 447

Synthesis and antibacterial activities of some fluorine containing arylfurylpropenones, pyrazolines and N- acetylpyrazolinet

B Shivarama Holla'a, M K Shivanandaa, P M Akberalib & M Shalini Shenoy'

' Department of P.G.Studies and Research in Chemistry, Mangalore University, Mangalagangotri-574 199, India bPlama Laboratories Ltd., 120 AlB Industrial Area, Baikampady, New Mangalore-575 011 , India.

CDepartment of Microbiology, KMC Mangalore-575 00 I, India.

Received 19 April 1999. accepted 26 October 1999

Several fluorine containing arylfurylpropenones 3 have been synthesized starting from arylfurfurals 1 and 2,4-dich loro-5-fluoroacetophenone 2. These arylfurylpropenones are then used for the synthesis of fluorine containing arylfurylpyrazolmes 4. The newly synthesized pyrazolines are then converted into their N-acetyl derivatives 5. The structures of these compounds have been confirmed on the basis of elemental analysis, IR, NMR and mass spectral studies. The mechanism for the fonnatlon of pyrazolines has been investigated. The above compounds are also subjected to antibacterial screening. !heir minimal inhibitory concentration (M IC) values indicate that some of these compounds exhibit excellent antibacterial activities.

The chemistry of chalcones and their heterocyclic analogues has been an interesting field of study for long time. The chalcones are used as building blocks for many heterocyclic ringsl. Chalcones are found to inhibit the growth of several pathogenic micro­organisms and fungi, whereas some of the chalcones are reported to possess important therapeutic properties such as hypertensive, anti peptic-ulcer activity etc. Heterocyclic analogues of chalcones are reported to possess bactericidal, bacteriostatic, cholerostatic activities2

-4.

In recent years, fluorinated acetophenones find an important place in the manufacture of drugs like Ciprofloxacin5

. Moreover, incorporation of fluorine can alter the course of the reaction as well as biological activities6

-8

. Further, the introduction of fluorine atom or CF) group into an organic molecule frequently provides compounds of pharmacological interest as compared to their non-fluorinated analogues. 5-Fluorouracil is a potential anticancer drug which can replace uracil in RNA, so disrupting its normal function. Besides, the use of fluorine containing CNS depressant drugs has increased tremendously and these are employed as antipsychotic and antianxiety agents, sedatives and hYl'notics, muscle relaxants and as a ppeti te depressants9

.

Several 1 3 5-trisubstituted pyrazolines are reported , , .. 10

to possess antiinflammatory, antlproteolytlc,

tpresented at the "Indo-German Symposium on Organic Synthesis-Growing Interface with Adjacent Sciences" held at II CT, Hyderabad-500 007, India during Sept. 27-28, 1996.

antibacterial, antifungal I I and insecticidal activities l2 . Also, l-aryl-2-pyrazolines are found to be useful as antioxidant composition in polymerslJ and in the treatment of cerebral edema l4 .

2-Pyrazolines having aryl substituents at positions-1,3 and 5 exhibit the phenomenon of fluorescence properties I 5. Pyrazolines exhibiting this phenomenon are extensively used as water soluble optical bleaches l 6

. Certain 2-pyrazolines attached to pyridine nng have been shown to exhibit fluorescent brightening properties I 7.

Pyrazolines attached to indole ring systems have been shown to exhibit monoamine oxidase inhibitor activit/ 8

. Several halonanilido pyrazolines are used in textile and cinematographic film industry and they are also found to possess bactericidal , insecticidal , fungicidal, anaesthetic, analgesic and antibacterial activities l9 . Besides, fluorinated pyrazoles and pyrazolmes find their applications as antifertility, anttbactenal and antifungal agents20

A number of nitrofurylpyrazoline derivatives2 1 were synthesized and tested for their antimicrobial properties. Some of them also find application as food preservatives especially in preserving fish sausages. However, the use of nitrofuryl pyrazolines as food preservatives has recently been di scouraged because of their toxicity. One of the methods adopted to bring down toxicity is to incorporate arylfurans instead of nitrofurans during synthesis.

Prompted by the varied biological activities of fluorinated compounds and pyrazolines, it was thought

HOLLA et at.: SYNTHESIS OF FLUORlNE CONTAINING ARYLFURYLPROPENONES 441

of interest to synthesize a new series of fluorine containing arylfuran pyrazoJines and to screen them for antibacterial properties.

For the present work, 1-(2,4-dichloro-5-fluorophenyl)-3-(5-aryl-2 ·furyl)-2-propen-l-ones 3 were prepared according to Claisen-Schmidt condensation by condensing 5-aryl-2-furfurals 1 with 2,4-dichloro-5-fluoroacetophenone 2 in the presence of sodium hydroxide. These propenones provided the suitable building block for the synthesis of 2-pyrazolines. These fluorine containing arylfurylpropenones were then treated with hydrazine hydrate to obtain 3-(2,4-dichloro-5-fluorophenyl)-5-(5-aryl-2-furyl)-2-pyrazolines 4. This reaction probably involved the intermediate formation of hydrazones and subsequent addition of NH across the carbon-carbon double bond of the propenone moiety. These pyrazolines were further subjected to acetylation in the presence of acetic anhydride to yield l-acetyl-3-(2,4-dichloro-5-fluorophenyl)-2-pyrazolines 5 (Scheme I). The structures of the newly synthesized compounds were characterized on the basis of elemental analysis, fR, NMR and mass spectral data.

The IR spectrum of 3a showed an absorption band at 1662 cm· l

, typical of a-unsaturated carbonyl functional group. The C=C bond absorption was seen at 1590 cm· l

. The absorption bands corresponding to nitro groups were sighted at 1540 and 1340 cm·1

respectively.

The 500 MHz IH NMR spectrum of 3b showed two doublets in the region, 8 6.62-6.63(J=3.5 Hz) and 6.76-6.77(J=3 .S Hz) which correspond to two (3-protons of furan ring. The olefin protons were seen as two doublets in the range, 87.41-7 .44(J=13 .5 Hz) and 7.S6-7.S8(J=14 Hz) respectively. The large value of coupling constant suggests the trans configuration. The p-bromophenyl protons appeared as two distinct doublets in the range 87.S1-7 .S2(J=8 .S Hz) and 7.53-7.54(J=8.S Hz) respectively each integrating for two protons. The aromatic protons of 2,4-dichloro-S­fluorophenyl protons were seen as three doublets in the ranges 87.07-7.09(JII. H=8.S Hz), 7.64-7 .66(JH.F ortho

=11.S Hz) and 7.4S-7.47(JH.F meta =7.0 Hz) respectively due to coupling with the neighbouring fluorine atom. Similarly, the SOO MHz IH NMR spectrum of 3e showed a doublet in the range 87.0-7.04 with a coupling constant of 16 Hz corresponding to olefinic proton. The other olefinic proton appeared as a doublet in the range 87.3S-7 .37(J=14 Hz). The two ~-protons of furan ring were seen as two closely spaced doublets

F

Ro-O-CHO + H,cJ-q-Cl (1)

Cl (2)

j 5'/. NoaH. EtOH a.

F

R-oJQ-CH~CHJ -P-Cl (3)

Cl

R Cl

(4 )

j Ao,O,.

F

R Cl

Scheme I

DMF

in the range 87.24-7.2S(J=3.S Hz) and 7.33-7 .34(J=4.0 Hz) respectively. A complex multiplet was observed in the region 87.44-7.50 which corresponds to 0-

chlorophenyl protons. A doublet was seen in the range

87.S9-7 .61(J=8 .0 Hz) which accounts for one of the 2,4-dichloro-S-fluorophenyl protons. This can be explained due to ortho coupling of proton with the neighbouring fluorine atom. Hov/ever, the meta coupling of proton with the fluorine atom produced a doublet in the range 7.98-7.99(J=6.0 Hz). The para coupling of two aromatic protons of 2,4-dichloro-S­fluorophenyl moiety resulted in two doublets in the range 87.76-7.77(JH.H para= 9 Hz) and S.04-S.06(JH.H

para= 9.S Hz) respectively.

442 INDIAN 1 CHEM, SEC B, JUNE 2000

Table I--Characterization data of 1 -(2,4-dichloro-S-fluoropheny~-(S-aryl-2-furyl)-2-propen-I-ones 3

Compd R m.p. Yield °C (%)

3a p-N02 198-200 78

3b p-Br 176-178 73 3c p-CI 114-116 90 3d m-N02 169-171 61

3e a-CI 119-121 89

3f a-N02 IOS-106 60

Mol fonnula

C I9H IOCI2FN04

C I9H IOBrCI2F02 CI9HIOCI3F02 C I9H IOCI2FN04

CI9HIOCI30 2

C I9H IOCI2FN04

Halochromism with conc.H2S0 4

Reddish pink colour Violet colour Violet colour Blood red colour Violet colour Red colour

Anal.(%N) Found(Calcd )

3.S0(3.4S)

3.46(3.4S)

3.S2(3.46)

IR(vmax in em-I): 3a, 1662(C=O), 1600(C=C), IS40(N02 aSym), I 340(N02 sym); 3b, 1682(C=O), 1600(C=C); 16S0(C=O), IS99(C=C), 3d, 1660(C=O), 1600(C=C), IS24(N02 asym), I 342(N02 sym); 3e, 1672(C=O), 1604(C=C). IH NMR (SOO MHz, DMSO-d6); 3e: 07.0-7.04(d, I H, 0Iefinic,.I=16.0 Hz), 7.24-7.2S(d, IH, furan 3H, J=3 .S Hz), 7.33-7.34(d, I H, furan 4H, .1=4.0 Hz), 7.3S-7.37(d, I H, olefinic, J= 14.0 Hz), 7.44-7.S0(complex multiplet, 4H, o-chlorophenyl protons), 7.59-7.6 1 (d, 1 H, 2,4-dichloro­S-fluorophenyl, J H_F ortho= 8.0 Hz), 7.98-7.99(d, I H, 2,4-dichloro-S-fluorophenyl, J H-F meta= 6.0 Hz), 7.76-7.77(d, I H, 2,4-dichloro-S­fluorophenyl , J II_II para= 9 Hz), 8.04-8.06(d, I H, 2,4-dichloro-S-fluorophenyl, J H-H para= 9.5 Hz); IH NMR(SOO MHz, DMSO-d6); 3b, 06.62-6.63(d, 1 H, furan 3H, J=3.S Hz), 6.76-6.77(d, I H, furan 4H, J=3.S Hz), 7.07-7.09(d, I H, 2,4-dichloro-S-fluorophenyl, J=8.S Hz), 7.41 -7.44(d, I H, olefi nic, J = 13 .S Hz), 7.S1-7.S2(d, I H, p-bromophenyl , J=8.S Hz), 7.S3-7.S4(d, I H, p-bromophenyl, J=8.5 Hz), 7.4S-7.47(d, 1 H, 2,4-dichloro-S-fluorophenyl , J II_F meta= 7.0 Hz), 7.64-7.66(d, I H, 2,4-dichloro-S-fluorophenyl, J II_F ortho= II .S Hz), 7.S6-7.S8(d, I H, olefinic, J= 14 Hz); 'H NMR(SOO MHz, DMSO-d6); 3d, 07.08-7. 12(d, IH, olefinic,J= IS .5 Hz), 7.2S-7.26(d, IH, furan 3H,.I=3.S Hz), 7.33-736(d, I H, olefinic, J= 16.0 Hz),7.492-7.497(d, I H, furan 4H, J=3.S Hz), 7.7S-7.80(m, 3H, m-nitro phenyl), 7.98-8 .0(d, I H, 2,4-dichloro-S­fluorophenyl , J H_F mcta= 6.5 Hz), 8.2-8.22(d, I H, 2,4-dichloro-S-fluorophenyl, JH-u= 8.25 Hz), 8.33-8 .34(d, 1 H, 2,4-dich loro-S -fluorophenyl , J II_Fortho=9.S Hz), 8.62-8.63(m, I H, m-nitrophenyl). Mass:3a, mlz 40S/407/409(M+/M+2/M+4, II %/8 .40/013.6%), 3S9(M-N02 1.1 %), 283(m-nitrophenyl, 4 .3%), 191 / 19311 9S(2,4-dichloro-S ­fluorobenzoyl cation, 12.40/0170/012.5%); 3b: mlz, 43814401442/444 (M+IM+21M+4/M+6, 640/0IS6 .80/0I7.So/0I3.4%), 3S9I36 1 (M-Br, 6.10/015%) 191 / 193/ 19S(2,4-dichloro-S-fluorobenzoyl cation, 1000/0164.80/01113%); 3c, mlz 394/396/398/400(M+ IM+ 2/M+41M+6, 1 000/0192.6%1 37.70/014.6%), 191 / 193/ 19S(2,4-dichloro-S-fluorobenzoyl cation, 33 .90/0I20.So/0I4.4%); 3d, mlz, 40Si407/409(M+/M+2/M+4 , 1000/01 67 .90/01 1 \.8%), 3S9(m-N02> S%), 283(m-nitrophcnyl, 2S%), 191 II 93/ 19S(2,4-dichloro-S-fluorobcnzoyl cation, 19.90/01 1 0.30/01 2.2%); 3e, mlz, 394/396/398/400(M+/M+2/M+4/M+6, 1000/0I86.80/0I33.60/0IS.3%), 3S9/36 I (M-C!, 210/01 11 .9%), 283(m-chlorophenyl, 2S%), 191 1193/ 19S(2,4-dichloro-S-fluorobenzoyl cation, 19.90/011 030/012.2%).

The mass spectra of compounds 3a, 3b, 3c, 3d and 3e showed molecular fons at m/z 405/407/409, 438/440/442/444, 394/396/398/400, 405/407/409 and 394/396/398/400 which correspond to the molecular formulae C,9H toClzFN04, CI9H IOBrCI2F02, C,9HtoChF02, C,9H toCI2FN04 and C I9HIOCh02 respectively. The formation of isotopic peaks were due to the presence of chlorine and bromine atoms. In the mass spectra of all these compounds, a common ion was observed at m/z 19111931195 which was explained due to the fragment ion viz ., 2,4-dichloro-5-fluorobenzoyl cation. The peaks observed at m/z 359 and 283 in the mass spectra of 3a and 3d were accounted for the formation of ions due to the loss of nitro and nitrophenyl radicals from the respective molecular ion. However, the peaks appeared in the mass spectra of 3b, 3c and 3e were due to the loss of bromine, chlorine and chlorine radicals respectively from the corresponding molecular ions. The spectral data of arylfurylpropenones are given in Table I .

The TR spectrum of pyrazoline 4c showed an

absorption band at 3300 cm-I corresponding to the pyrazoline NH group. The absorption bands at 1590 and 1500 cm-I are attributed to the groups C=N str. and N-N str. respectively. The absence of carbonyl band ; Iearly supported the formation of 2-pyrazoline system .

In the 400 MHz PMR spectrum of the compound 4a, the pyrazoline NH proton resonated at 88.6. The CH2 protons of the pyrazoline ring appeared as two doublets of doublet in the range 82.78-2.84(1=9.7 Hz, 9.7 Hz) and 3.59-3 .66(J=11.24 Hz, J=11.24 Hz) respectively due to multiple coupling involving both geminal and vicinal protons. The CI r proton also appeared as a doublet of doublet at 86.62-6.67(J=1O.19 Hz, J=10.19 Hz) due to vicinal coupling with the two magnetically non-equivalent protons of the methylene group at position-4 of the pyrazoline ring. The furan ring protons were seen as two closely spaced doublets at 86.87-6.88(1=3.9 Hz) and 7.39-7.40(J=3 .9 Hz) respectively integrating for two protons. The aromatic protons signals of the chlorofluorophenyl moiety appeared as two doublets at

HOLLA et al.: SYNTHESIS OF FLUORINE CONTAINING ARYLFURYLPROPENONES 443

Table Il---Olaracterization data of 3-(2,4-diehloro-5-tluorophenyl)-5-(5-aryl-2-furyl)-2-pyrazolines 4 and N-aeetylpyrazoline Sa

Compd R m.p. Yield Mol. Anal(%N) °C (%) formula Found (Caled )

4a p-N02 170-172 71 C'9H12CI2FN)O) 10.08(10.02) 4b p-Br 145-147 68 C'9H'2BrCI2N20 6.27(6.19) 4c p-CI 100-102 70 C'9H '2CI)FN2O 6.78(6.86) 4d m-N02 150-152 69 C'9H12ChFN)O) 9.96( 10.02) 4e o-CI 103-105 68 C'9H '2CI)FN2O 6.92(6,86) 4f o-N02 101-103 67 C'9H I2CI2FN)O) 10.11(10.02) Sa p-N02 178-180 93 C2, H'4CI2FN)04 9.05(9.11 )

lR(vmax in em"): 4a, 3300(NH), I 580(N02 asym), I 320(N02 sym)

Sa; I 680(C=O str.), I 540(N02 asym) & I 360(N02 sym ); 'H NMR (400 MHz, DMSO-d6); 4a: 82.78-2.84(dd, IH, CH2, J=9.7 Hz, 9.2 Hz), 3.59-3.66(dd, I H, CH2, .I=1 1.24 Hz, 11.24 Hz), 6.62-6.67(dd, I H, CH,.I= I 0.19 Hz), 6.87-6.88(d, I H, furan 3H, J=3.9 Hz), 7.39-7.40(d, I H, furan 4H, .1=3.9 Hz), 8.6(s, I H, pyrazoline NH), 7.50-7.52(d, I H, ehlorotluorophenyl , .1=12.59 Hz), 7.83-7.87(d, I H, ehlorotluorophenyl, .1=8.38 Hz), 7.95-7.98(d, 2H, p-nitrophenyl, .1=8.8 Hz), 8.27-8.29(d,2H p-nitrophenyl, .1=8.8 Hz)Mass: 4a, mlz 41 9142 1/423(M+IM+2/M+4,

~ 32.60/<>"19.20/<>"2.7%), 390/392/394(M+ -N-NH, 67.8%/ 16.30/<>"9.3%), 214(p-nitrophenylfuro nitrile, 6.2%), 189/ 191 /193(2,4-diehloro-5-tluorobenzonitrile,7.30/<>"80/<>"8 .6%), 389/391 /393(M+-NO, 5.90/<>"67.80/<>"42.1 %), 361 /363/365(M+-NO & CO, 35.50/<>" 10.50/<>"6.3%); 4b, mlz,

4521454/456 (M+1M+2IM+4, 6.0°/<>"7.4%/3.3%), 423/425/427(M+-NNH, 19.7%17.1 %17.6%), 247/249(p-bromophenylfuronitrile, 7.9%/3.2%), I 89/1911193(2,4-diehloro-5-tluorobenzonitrile, 4.8%/5.30/<>"6.7%); 4c, mlz, 4081410/412 (M+IM+21M+4, 7.5%/8.30/<>"3.7%), 3791381/383(~-N-NH ,5 . 5%15 . 3 %/5 . 2%), 203/205(p-ehlorophenylfuronitrile, 7.10/<>" 12.1 %), I 891 19 III 93(2,4-diehloro-5-tluorobenzonitrile, 8.90/<>"69.30/<>"3\.7%); 4f, 214(o-nitrophenylfuronitrile, 4.4%), 18911911193 (2,4-diehloro-5-tluorobenzonitrile, 3.9%/8.7%1 11.4%); Sa, mlz, 461 /4631465 ~1M+2IM+4, 12°/<>"7.90/<>" 1.5%), 418/420/422(M+-Ae, 35%/8.2%/4.5%), 214(p-nitrophenylfuronitrile, II.I %), I 89/ 191 /193(2,4-diehlofo-5-tluorobenzonitrile, 3.10/<>"3.60/<>"3.2%), 415/417(M-N02, 10/<>" 1.2%), 403/405(M-NO & CO, 11.5%/8.3%), 390(M-Ae-N2, 13 .1 %), I 8911911193(2,4-diehloro-5-tluorobenzo-nitrile, 3.1 %/3.6%/3.4%), 214(p-nitrophenylfuronitrile, 11 .1 %)

87.50-7.52(J=1.2.59 Hz) and 7.83-7.87(J=8.38 Hz) owing to ortho and meta coupling with the neighbouring fluorine atom. The aromatic protons of p­nitrophenyl residue were seen as two distinct doublets at 87.95-7.98 and 8.27 -8.29 respectively with a coupling constant of 8.8 Hz.

The mass spectrum of compound 4a showed a fairly intense molecular ion peak at m/z 419/4211423 along with M+2 and M+4 peaks corresponding to the molecular formula C19H 12ChFN)O). The ~ -N-NH peak was observed at m/z 390/392/394. A characteristic molecular ion peak of p­nitrophenylfuronitrile was observed at m/z 214 typical of p-nitrophenylfuran derivatives. The peak appeared at m/z 189/1911193 could be attributed to the molecular ion of 2,4-dichloro-5-fluorobenzonitrile obtained by the fragmentation of the parent molecular ion. Fragmentation of this type is also typical of nitrogen containing heterocycles. The mass spectrum of acetylpyrazoline 5a showed a molecular ion peak at m/z 4611463/465 along with M+2 and M+4 peaks corresponding to the molecular formula C21H14ChFN304, thus, confirming the structure assigned to it. The base peak was observed at m/z 43 corresponding to CHrC=O moiety. This also confumed the formation of acetyl derivative. The molecular ion underwent fragmentation to give ions at

m/z 418 and 420 which could arise due to the loss of CH3CO from the molecular ion. The peaks were also observed at m/z 415/417(M-N02)' 403/405(M-NO & CO), 390(M-43-N2)' 1891l911193(2,4-dichloro-5-fluorobenzo nitrile) and 214(the ubiquitous peak of p­nitrophenylfuronitrile). The mass spectral data of pyrazolines are given in Table II and the typical mass spectral fragmentation pattern of 5a is depicted in Scheme II.

Mechanism The formation of pyrazolines 4 can be rationalized

on the basis of two reaction pathways as shown in Scheme III. The first reaction pathway involves a Michael addition of hydrazine on the arylfurylpropenone 3, followed by a 5-Exo-Trig. ring cyclization and dehydration. This is an allowed process according to Baldwin's rules22 .

The second route involves the initial formation of a hydrazone followed by a subsequent 5-Endo-Trig. ring cyclization, which according to Baldwin's rules is an unfavourable reaction. However, due to the tautomerism of pyrazolines, the product obtained by either of the mechanisms is the same pyrazoline 4.

Antibacterial activity All the newly synthesized arylfurylpropenones 3,

444 INDIAN] CHEM, SEC B, JUNE 2000

OzN

m/z 461/463

(12 .0.'°/7.9.'0 )

/ -o-Q-<J~ I I l +

- N

m/z 419/421/423 (35.0.'./21.2 010) .

m/z 272 (3 .6 01.)

1-43(A"

I eocH:! F/ Ct~

Cl

\ o N-0-CJ--<1~ I I

2 '0 - N

ttl

OzN~ ttl

ml z 202 (7.2·10) m/z 229 (5.8°10)

+ + ml z 229 (5 . 8°10)

O2 N-Q--CJ--CSN

F

Ct-Q-C'N Cl

m /z 2f4(111°W m/z 189 (3.1"10)

m/z 160 (G . 4°10)

Moss spectral fragmentation pattern of 1-acetyl pyrazolinc

&:hcmc II

arylfuryl pyrazolines 4 and N-acetylpyrazolines Sa were screened for their antibacterial activity against E. coli, S aureus, P. aeruginosa and B. sub/ilis. Their minimum inhibitory concentrations (MIC values) were determined according to serial dilution method. Furacin was used as a standard drug for comparison. The results of such studies are given in Table In.

TIle screening data indicate that among the arylfurylpopenones tested, compound 3b carrying p-

bromo substituent showed excellent antibacterial activity against S . aureus, while compound 3d possessing m-nitro substituent found to exhibit excellent activity against E. coli and P. aeruginosa . The compound 3f carrying o-nitro group possessed greater degree of activity against B. sublilis. Also, compounds 3a, 3b, 3c, 3d, 3e and 3f showed a greater degree of antibacterial activity especially against S aureus, P. aeruginosa and B. subtilis than that of

HOLLA et al.: SYNTHESIS OF FLUORINE CONTAINING ARYLFURYLPROPENONES 445

R~n ~A V "0""'" ""CH= CH -C .>=J CI

CI

(3 )

Via Michael addition Via Schiff bose formation

R~n U "0/ )CHbc~F - ( If CI

If -H2N - N

CI

tS-Endo_r",

R R

CI CI

CI (4)

Mechanism of pyrazoline formation (4)

Scheme III

Furacin. Among the pyrazolines tested for the above activity, compound 4a carrying p-nitro group showed good antibacterial activity against S. aureus, while compound 4f carrying o-nitro substituent possessed good activity against P. aeruginosa compared to Furacin. Further, antibacterial activity of compound 4a was found to increase especially against E. coli and P. aeruginosa when it is converted into N-acetyl derivative. It is further observed that in general, arylfurylpropenones were found to be more active than corresponding arylfurylpyrazolines. Thus, it was concluded that compounds 3a, 3b, 3c, 3d, 3e, 4a and 5a stand to be promising antibacterial agents.

Experimental Section Melting points were determined by capillary method

and are uncorrected. IR spectra (KBr) were recorded on a Perkin-Elmer Infrared spectrophotometer; IH NMR in OMSO-d6 on a JEOL GSX 400 spectrometer and mass spectra on a Jeol JMS 0-300 mass spectrometer operating at 70 eV. Arylfurfurals were synthesized through Meerwein reaction. Purity of compounds were checked by TLC on silica gel plates employing benzene:methanol (2: 1) solvent system and iodine was used as a visualizing agent.

Preparation of 1-(2,4-dichloro-5-fluorophenyl)-3-(5-aryl-2-furyl)-2-propen-l-ones 3: General pro­cedure 2,4-0ichloro-5-fluoroacetophenone (2, 0.01 lvf) was dissolved in ethanol. To this were added NaOH solution (5 mL, 30%) and suitably substituted arylfurfuraldehyde (1, 0.01 M) were added to the resulting solution with continuous stirring. The clear

446 INDIAN 1 CHEM, SEC B, JUNE 2000

Table III-Antibacterial activity data of arylfurylpropenones 3, pyrazolines 4 and N-acetylpyrazo line 5

Compd Minimum Inhibitory Concentration (jlg/mL) E.coli Saureus P.aeruginosa B.sulilis

3a 6 6

3b 6 1.5

3c 6 6

3d 3 6

3e 12.5 6

3f 12.5 6

4a 12.5 6

4b 6 12.5

4c 12.5 12.5

4d 12.5 12.5

4e 12.5 12.5

4f 6 25

Sa 6 6

Furacin 6 12.5

(Standard)

E. coli= Escherichia coli; S aureus= Staphylococcus aureus P.aeruginosa= Pseudomonas aeruginosa; B. subtilis= Bacillus subtilis

solution so obtained was left for 4 hr at room temperature with stirring and was allowed to stand overnight. The solid separated was filtered off, dried and recrystallized from a mixture of dimethyl­formamide and ethanol.

Preparation of 3-(2,4-dichloro-5-fluorophenyl)-5-(5-aryl-2-furyl)-2-pyrazolines 4: General procedure. 1-(2,4-Dichloro- 5-fluorophenyl)-3-(5-aryl-2- furyl)-2-propen-l-one (3, 0.01 M) was dissolved in dioxane (25 mL) and hydrazine hydrate (90%, 5 mL) was added to this solution dropwise. The reaction mixture was heated under reflux for 4 hr. Excess of solvent was distilled off. It was cooled and poured onto crushed ice. The resulting pyrazolines were collected by filtration and recrystallized from a mixture of dime­thylformamide and ethanol.

Preparation of l-acetyl-3-(2,4-dichloro-5-fluoro­phenyl)-5-(5-aryl-2-furyl)-2-pyrazolines 5: General procedure. A solution of 3-(2,4-dichloro-5-fluoro­phenyl)-5-(5-aryl-2-furyl)-2-pyrazolines (4, 0.01 M) in acetic anhydride (10 mL) was heated under reflux for 3 hr. The reaction mixture was cooled and poured onto crushed ice in order to decompose excess of acetic anhydride. The solid material obtained was collected by filtration and recrystallized from a mixture of dimethylformamide and ethanol.

Acknowledgement Thanks are due to Head, RSIC, CDRl, Lucknow for

providing mass spectral and microanalysis data, Head, RSIC, lIT Madras, Head, RSIC, Panjab University, Chandigarh for providing IR and NMR spectra of

6 6 6 6 6 6 3 6 6 6 6 3

12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5

6 12.5 6 6

12.5 12.5

compounds. The authors are also thankful to Prof. Michael J. Levine for providing 500 MHz PMR spectra of compounds reported herein and Prof. Ananthakrishna, Head, Department of Microbiology, KMC, Mangalore for providing necessary facilities of the College for antibacterial screening. Further, the grant received from US Public Health Service Grant DE 08240 is gratefully acknowledged. One of the authors (MKS) is grateful to CSIR, New Delhi for granting Senior Research Fellowship.

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