terphenyl is a common structural motif found in various natural products , largely isolated from microbes and mushrooms . in recent years , it has been reported that some terphenyls exhibit considerable biological activities , for example , potent anticoagulants , immunosuppressants , antithrombotic , neuroprotective , specific 5-lipoxygenase inhibitory , and cytotoxic activities . because of their promising biological activities and important properties , terphenyls have been produced increasing research interest . recently we have reported a new and simple method for the preparation of ester derivative of terphenyl starting from 4,4-difluoro chalcone . the esters can be easily converted into the corresponding carbohydrazide by the reaction with hydrazine hydrate . hydrazides and related compounds have been described as useful precursors for the assembly of various heterocyclic rings . a large number of hydrazides are reported to be of biological interest [ 5 , 6 ] , while oxadiazole derivatives and thiosemicarbazides have been reported to possess antibacterial [ 7 , 8 ] , antifungal [ 9 , 10 ] , and other biological activities . furthermore , a number of substituted thiazolines and thiazolidinones are found to exhibit appreciable antimicrobial activities [ 1115 ] .   in the course of investigation , we have found that 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carbohydrazide is an excellent building block for the synthesis of numerous heterocyclic systems . in view of the pharmacological importance of terphenyls and in continuation of our work on synthesis of various derivatives of 4,4-difluoro chalcone [ 1623 ] , it was decided to prepare new functionalized terphenyl derivatives by using 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carbohydrazide as the key intermediate and to study their biological activities . a novel terphenyl derivative , ethyl 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carboxylate 3 , was synthesized by the oxidative aromatization of cyclohexenone derivative of 4,4-difluoro chalcone using chloramine - t . the ester 3 was converted into the corresponding carbohydrazide 4 in high yield by the reaction with hydrazine hydrate ( scheme 1 ) . in the ir spectrum of carbohydrazide 4 broad stretching band at 3290  cm was due to nh while strong stretching band at 1672  cm was attributed to carbonyl . h nmr spectrum showed two singlets at  9.19 ppm and  4.18  ppm which were accounted for nh2 and nh protons . the mass spectrum of 4 showed a molecular ion peak at m / z 341.0 which confirmed its molecular weight . the carbohydrazide is a versatile key intermediate for the synthesis of several heterocyclic systems such as pyrazoles , thiazoles , 1,3,4-oxadiazoles , and 1,2,4-triazoles [ 24 , 25 ] . hence , the carbohydrazide 4 was treated with various reagents to afford pyrazole and 1,3,4-oxadiazole derivatives ( scheme 2 ) . condensation reaction of carbohydrazide 4 with dicarbonyl compounds , namely , acetylacetone and ethyl acetoacetate , in the presence of catalytic amount of triethylamine afforded the corresponding substituted pyrazole derivatives 5 and 6 , respectively . the ir spectrum of pyrazole 5 showed the presence of vibrations at 2926  cm due to methyl group . the h nmr spectrum of 5 showed two singlets at  2.29 and 2.70  ppm due to three each protons of two methyl groups at c-3 and c-5 carbon of pyrazole ring , respectively , and hence confirming the presence of 3,5-dimethyl-1h - pyrazole moiety . similarly , in the ir spectrum of pyrazole 6 , vibrations at 1654  cm indicates the presence of carbonyl group of the pyrazolone nuclei . singlets at  2.84 and 2.03  ppm in the h nmr spectrum were observed for the methyl and methylene protons of the pyrazolone moiety . cyclization to the oxadiazoles was carried out by treating the carbohydrazide 4 with triethyl orthoformate / toluene , cyanogen bromide / ethanol and with aromatic acids / phosphorous oxychloride . the ir spectra of oxadiazoles 7 and 9 showed the absence of vibrations due to nh and nh2 groups . their h nmr spectra also indicated the absence of nh protons , thus confirmed the cyclization reaction . in the ir spectrum of oxadiazole 8 , a stretching vibration observed at 3385  cm which indicates the presence of amino group . a singlet at  6.93  ppm in the h nmr spectrum of 8 confirmed the presence of nh2 group and hence proved that ring closure starting from carbohydrazide 4 resulted in the formation of 5-amino-1,3,4-oxadiazole moiety . thus , condensation of carbohydrazide 4 with aromatic aldehydes in absolute ethanol in presence of few drops of concentrated hydrochloric acid afforded the corresponding schiff bases 10a  c . the schiff bases 10a  c thus obtained were cyclized into 1,3,4-oxadiazole derivatives 11a  c by refluxing them with acetic anhydride ( scheme 3 ) . ir spectra of 10a  c , showed an nh stretching band at around 3329  cm and a carbonyl absorption band near 1647  cm . the h nmr spectrum of 10c , as an example , showed a singlet signal at  8.15  ppm corresponding to ch of the benzylidene group and another singlet signal at  11.71  ppm due to nh proton , hence confirming the formation of schiff base hydrazone . the ir spectra of compounds 11a  c had different characteristics since they showed no n h stretching bands , but carbonyl stretching near 1770  cm which could be attributed to the carbonyl of acetyl group . h nmr spectra of 11a  c showed a singlet in the spectra in the range  6.416.52  ppm indicating ch resonance of the oxadiazoline ring which is in accordance with the reported values found in the literature . the treatment of hydrazides with carbon disulfide in the presence of alkali hydroxide was a general method leading to the formation of 1,3,4-oxadiazole-2-thione derivatives . as the starting material , carbohydrazide 4 was used for the synthesis of 1,3,4-oxadiazole-2-thione derivative 12 ( scheme 4 ) . the ir spectrum of compound 12 showed a sharp absorption band at 3224  cm representing nh group . its h nmr spectrum displayed a signal at  14.53  ppm due to the nh proton , while no signal representing a hydrazide structure appeared . the 4-amino-1,2,4-triazole-3-thione derivative 13 was synthesized starting from compound 12 by treating it with hydrazine hydrate . the ir spectrum of compound 13 showed two sharp absorption bands at 3373  cm and 3259  cm representing nh and nh2 groups . the singlet signal integrating two protons seen at  5.45  ppm in the h nmr spectrum of compound 13 was attributed to the nh2 group . furthermore , an additional singlet was observed due to the nh group at  13.54  ppm integrating one proton . mannich reaction of 1,3,4-oxadiazole-2-thione derivative 12 with secondary amines and formaldehyde in absolute ethanol at room temperature yielded the desired compounds 14a  c . when compared with the compound 12 , the ir spectra of mannich bases 14a  c showed the absence of nh group . their h nmr spectra also supported the proposed structure as there was no signal corresponding to nh proton . however , it has been established that under the action of alkyl halides s - substitution took place instead of n - substitution . the mass spectrum of 15c showed a molecular ion peak at m / z 555.1 which reveals that the compound not only s - alkylated but also o - alkylated , because of the presence of phenolic group . furthermore , the intermediate thiosemicarbazide derivative  16 representing a versatile building block for the synthesis of new heterocycles incorporating thiazole , imidazole , and triazole nucleus was synthesized by heating the carbohydrazide 4 with potassium thiocyanate in the presence of hydrochloric acid [ 28 , 29 ] ( scheme 5 ) . the h nmr spectrum of 16 exhibited singlet signals at  6.96  ppm and 8.19  ppm due to nh2 protons as one of the proton involved in intramolecular hydrogen bonding with carbonyl group ; two protons were unequal . in addition to that , it showed two singlets at  9.57 and 10.45  ppm due to two nh protons . the ir spectrum of 16 exhibited two sharp absorption bands at 3464  cm and 3329  cm representing nh and nh2 groups . the thiazole derivatives 17a  c was synthesized by the treatment of thiosemicarbazide derivative 16 with different phenacyl bromides in boiling ethanol . the ir spectra of thiazoles 17a  c showed absorption band at 3331  cm representing nh groups . its h nmr spectra exhibited two singlets in the region  9.410.5  ppm for hydrazide ( nh ) protons , and hence confirming the formation of thiazole moiety . compound 16 was cyclized via oxidative cyclization in basic medium ( 10% naoh ) , under reflux condition with subsequent acidification to give 1,2,4-triazole-3-thiol derivative 18 . further , reflux of compound 16 with monochloroacetic acid and anhydrous sodium acetate in glacial acetic acid afforded a product identified as 2-imino-4-oxo-1,3-thiazolidine derivative 19 ( scheme 5 ) . the structure of the synthesized products 18 and 19 was established on the basis of spectral data . for example , in compound 18 , the absence of absorption band of carbonyl group in ir spectrum and lack of h nmr resonances observed with nh and nh2 functions proved the intramolecular cyclization of compound 16 resulted in the formation of 1,2,4-triazole ring . similarly , ir spectrum of thiazolidine derivative 19 showed an absorption band at 1724  cm representing carbonyl group of imidazolidinone moiety . a singlet at  3.88  ppm present in the h nmr spectrum of 19 indicated the two protons of methylene group of imidazolidinone moiety , in addition to a singlet at  4.10  ppm due to sh proton and another singlet at  10.59  ppm due to that nh proton confirmed the presence of imidazolidinone moiety . the newly synthesized compounds were screened for their antibacterial activity against escherichia coli ( attc-25922 ) , staphylococcus aureus ( attc-25923 ) , pseudomonas aeruginosa ( atcc-27853 ) , and klebsiella pneumoniae ( recultured ) bacterial strains by serial plate dilution method [ 30 , 31 ] . compound 12 was found to be the most active derivative against escherichia coli , pseudomonas aeruginosa , and klebsiella pneumoniae at mic value of 6.25  g / ml among the tested compounds and showed the same potency with ciprofloxacin . the compounds 3 , 4 , 5 , 6 , 16 , 17a , 17b , and 17c were found to be active against all the tested microorganisms at mic value of 12.5  g / ml . the high activity of 12 was due to the presence of 1,3,4-oxadiazole-2-thione moiety containing free nh group . also the derivatives containing hydrazide moiety ( 4 , 16 , 17a , 17b , 17c ) , ester group ( 3 ) , and pyrazole moiety ( 5 & 6 ) were helped to inhibit the growth of the microorganisms . newly prepared compounds were screened for their antifungal activity against aspergillus flavus ( ncim no . 902 ) , penicillium ( s. aureus ) ( recultured ) , and trichophyton mentagrophytes ( recultured ) in dmso by serial plate dilution method [ 32 , 33 ] . compounds 6 , 8 , and 10b were found to be the most active derivatives against all the tested microorganisms at an mic value of 6.25  g / ml among the tested compounds , and showed the same potency with itraconozole . although compounds 9a , 9c , 10a , 11a , 11b , 11c , 17a , and 19 showed activity having mic value of 12.5  g / ml against selected microorganisms , they exhibited lower potencies than the compared standard drug . hence , it could be concluded that different functionality present in the molecules contributed to the antifungal activity in different manner comparable with that of standard drug tested . a rapid , simple , and inexpensive method to measure antioxidant capacity of substances involves the use of the free radical , 2,2-diphenyl-1-picrylhydrazyl ( dpph ) . dpph is widely used to test the ability of compounds to act as free radical scavengers or hydrogen donors . this simple test further provides information on the ability of a compound to donate electrons during antioxidant action . the radical scavenging mechanism is based on the transfer of acidic h - atom from the compound to dpph radical to form dpph - h .   among the tested compounds , many compounds showed significant radical scavenging capacity due to the presence of phenolic hydrogen in the parent molecule . compounds 12 and 13 showed good radical scavenging capacity while compounds 9a , 9b , 14a , 14b , 15c , and 16 exhibited moderate radical scavenging capacity with concentration of 1  mg / ml in comparison with the standard glutathione . the good radical scavenging capacity of compounds 12 and 13 was due to the presence of acidic protons in the oxadiazole moiety . the variation exhibited in dpph scavenging capacity could be attributed to the effect of different moiety present in the compounds . reducing power is associated with antioxidant activity and may serve as a significant reflection of the antioxidant activity . compounds with reducing power indicate that they are electron donors and can reduce the oxidized intermediates of lipid peroxidation processes , so that they can act as primary and secondary antioxidants . substances , which have reduction potential , react with potassium ferricyanide ( fe ) to form potassium ferrocyanide ( fe ) , which then reacts with ferric chloride to form ferrous complex that has an absorption maximum at 700  nm . increased absorbance of the reaction mixture indicates the increased reducing power . reducing power assay is expressed in effective concentration ( mg / ml ) equivalent to 0.5 absorbance glutathione . among the tested compounds , many compounds showed significant reducing power capacity . compounds 4 , 12 , 13 , and 16 showed good reducing power capacity while compounds 5 , 8 , 10b , 17a , 17b , 17c , 18 , and 19 exhibited moderate reducing power capacity in comparison with the standard glutathione . the good reducing power capacity of these compounds was due to the presence of free nh group in the molecules . new functionalized terphenyl derivatives incorporating various heterocyclic rings are prepared by using 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carbohydrazide as a key intermediate derived from 4,4-difluoro chalcone as a versatile synthone . the majority of the tested compounds exhibited significant antimicrobial activity and some of them showed good dpph scavenging activity . hence this study has widened the scope of developing easy method to synthesize fluorinated functionalized terphenyl derivatives as promising antimicrobial and antioxidant agents . the purity of the compounds was confirmed by thin layer chromatography using merck silica gel 60 f254 coated aluminium plates . ir spectra were recorded on shimadzu - ftir infrared spectrometer in kbr ( max in cm ) . hnmr ( 400  mhz ) spectra were recorded on a bruker amx 400 spectrometer , with 5  mm pabbo bb-1h tubes with tms as internal standard . elemental analysis was carried out by using vario el - iii ( elementar analysensysteme gmbh ) . synthesis of ethyl 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carboxylate ( 3 ) ethyl 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carboxylate ( 3 ) was synthesized by the oxidative aromatization of ethyl 4,6-bis(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate ( 2 ) using chloramine - t , which in turn was prepared by the condensation of ethyl acetoacetate to the 4,4-difluoro chalcone ( 1 ) according to the methods described in our previous work . ethyl 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carboxylate ( 3 ) was synthesized by the oxidative aromatization of ethyl 4,6-bis(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate ( 2 ) using chloramine - t , which in turn was prepared by the condensation of ethyl acetoacetate to the 4,4-difluoro chalcone ( 1 ) according to the methods described in our previous work . synthesis of 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carbohydrazide ( 4 ) a mixture of ester 3 ( 17.7  g , 0.05  mol ) and hydrazine hydrate ( 10  ml , 99% ) in absolute ethanol ( 60  ml ) was heated under reflux for 16  h and cooled at room temperature . ir ( kbr , v  cm ) : 3290 ( nh ) , 1672 ( c = o ) , 1219 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 4.18 ( s , 2h , nh2 ) , 6.997.69 ( m , 10h , ar h ) , 9.19 ( s , 1h , nh ) , 9.87 ( s , 1h , oh ) . lcms : m / z 341.0 ( m+1 ) . c h n analysis ; calculated for c19h14f2n2o2 : c , 67.05 ; h , 4.15 ; n , 8.23 . found : c , 67.02 ; h , 4.16 ; n , 8.20 . 
   a mixture of ester 3 ( 17.7  g , 0.05  mol ) and hydrazine hydrate ( 10  ml , 99% ) in absolute ethanol ( 60  ml ) was heated under reflux for 16  h and cooled at room temperature . ir ( kbr , v  cm ) : 3290 ( nh ) , 1672 ( c = o ) , 1219 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 4.18 ( s , 2h , nh2 ) , 6.997.69 ( m , 10h , ar h ) , 9.19 ( s , 1h , nh ) , 9.87 ( s , 1h , oh ) . lcms : m / z 341.0 ( m+1 ) . c h n analysis ; calculated for c19h14f2n2o2 : c , 67.05 ; h , 4.15 ; n , 8.23 . . 
 synthesis of ( 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)(3,5-dimethyl-1h - pyrazol-1-yl)methanone ( 5 ) to a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and acetylacetone ( 1.0  g , 0.01  mol ) in ethanol ( 20  ml ) triethylamine ( 1  ml ) was added , and the mixture was refluxed for 10  h. the precipitated solid was filtered off and recrystallized from ethanol . yield 52% ; m.p 166168c . 3327 ( oh ) , 2926 ( c  h ) , 1604 ( c = n ) , 1215 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.29 ( s , 3h , ch3 ) , 2.70 ( s , 3h , ch3 ) , 6.28 ( d , 1h , ch ) , 6.957.71 ( m , 10h , ar h ) , 9.70 ( d , 1h , oh ) . lcms : m / z 407.0 ( m+1 ) . c h n analysis ; calculated for c24h20f2n2o2 : c , 71.28 ; h , 4.49 ; n , 6.93 . found : c , 71.24 ; h , 4.47 ; n , 6.91 . 
   to a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and acetylacetone ( 1.0  g , 0.01  mol ) in ethanol ( 20  ml ) triethylamine ( 1  ml ) was added , and the mixture was refluxed for 10  h. the precipitated solid was filtered off and recrystallized from ethanol . yield 52% ; m.p 166168c . ir ( kbr , v  cm ) : 3327 ( oh ) , 2926 ( c  h ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.29 ( s , 3h , ch3 ) , 2.70 ( s , 3h , ch3 ) , 6.28 ( d , 1h , ch ) , 6.957.71 ( m , 10h , ar h ) , 9.70 ( d , 1h , oh ) . lcms : m / z 407.0 ( m+1 ) . c h n analysis ; calculated for c24h20f2n2o2 : c , 71.28 ; h , 4.49 ; n , 6.93 . found : c , 71.24 ; h , 4.47 ; n , 6.91 . 
 synthesis of 2-[(4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)carbonyl]-5-methyl-2,4-dihydro-3h - pyrazol-3-one ( 6 ) to a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and ethyl acetoacetate ( 1.3  g , 0.01  mol ) in ethanol ( 20  ml ) triethylamine ( 1  ml ) was added , and the mixture was refluxed for 12  h. the precipitated solid was filtered off and recrystallized from ethanol . ir ( kbr , v  cm ) : 3055 ( oh ) , 2985 ( c - h ) , 1654 ( c = o ) , 1608 ( c = h nmr ( 400 mhz , dmso - d6 ,   ppm ) : 2.03 ( s , 2h , ch2 ) , 2.84 ( s , 3h , ch3 ) , 7.047.72 ( m , 10h , ar h ) , 10.23 ( s , 1h , oh ) . lcms : m / z 407.1 ( m+1 ) . c h n analysis ; calculated for c23h16f2n2o3 : c , 67.98 ; h , 3.97 ; n , 6.89 . found : c , 67.94 ; h , 3.97 ; n , 6.84 . 
   to a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and ethyl acetoacetate ( 1.3  g , 0.01  mol ) in ethanol ( 20  ml ) triethylamine ( 1  ml ) was added , and the mixture was refluxed for 12  h. the precipitated solid was filtered off and recrystallized from ethanol . ir ( kbr , v  cm ) : 3055 ( oh ) , 2985 ( c - h ) , 1654 ( c = o ) , 1608 ( c = h nmr ( 400 mhz , dmso - d6 ,   ppm ) : 2.03 ( s , 2h , ch2 ) , 2.84 ( s , 3h , ch3 ) , 7.047.72 ( m , 10h , ar c h n analysis ; calculated for c23h16f2n2o3 : c , 67.98 ; h , 3.97 ; n , 6.89 . synthesis of 4,4-difluoro-4-(1,3,4-oxadiazol-2-yl)-1,1:3,1-terphenyl-5-ol ( 7 ) a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and triethyl orthoformate ( 1  ml ) in toluene ( 60  ml ) was heated under reflux for 10  h. the excess solvent was evaporated and the reaction mass was cooled to room temperature . ir ( kbr , v  cm ) : 3149 ( oh ) , 1620 ( c = n ) , 1232 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm 7.127.79 ( m , 10h , ar h ) , 9.23 ( s , 1h , ch ) , 10.57 ( s , 1h , oh ) . c h n analysis ; calculated for c20h12f2n2o2 : c , 68.57 ; h , 3.45 ; n , 8.00 . found : c , 68.54 ; h , 3.44 ; n , 7.98 . 
   a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and triethyl orthoformate ( 1  ml ) in toluene ( 60  ml ) was heated under reflux for 10  h. the excess solvent was evaporated and the reaction mass was cooled to room temperature . ir ( kbr , v  cm ) : 3149 ( oh ) , 1620 ( c = n ) , 1232 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm 7.127.79 ( m , 10h , ar h ) , 9.23 ( s , 1h , ch ) , 10.57 ( s , 1h , oh ) . lcms : m / z 351.0 ( m+1 ) . c h n analysis ; calculated for c20h12f2n2o2 : c , 68.57 ; h , 3.45 ; n , 8.00 . synthesis of 4-(5-amino-1,3,4-oxadiazol-2-yl)-4,4-difluoro-1,1:3,1-terphenyl-5-ol ( 8) a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and cyanogen bromide ( 1.57  g , 0.015  mol ) in absolute ethanol ( 20  ml ) was refluxed for 5  h. the reaction mass was cooled to room temperature and neutralized with saturated sodium bicarbonate solution . ir ( kbr , v  cm ) : 3385 ( nh2 ) , 3116 ( oh ) , 1600 ( c = n ) , 1217 ( c  f ) . h nmr ( 400 mhz , dmso - d6 ,   ppm ) : 6.93 ( s , 2h , nh2 ) , 7.137.77 ( m , 10h , ar h ) , 10.44 ( s , 1h , oh ) . lcms : m / z 366.0 ( m+1 ) . c h n analysis ; calculated for c20h13f2n3o2 : c , 65.75 ; h , 3.59 ; n , 11.50 . found : c , 65.73 ; h , 3.57 ; n , 11.47 . 
   a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and cyanogen bromide ( 1.57  g , 0.015  mol ) in absolute ethanol ( 20  ml ) was refluxed for 5  h. the reaction mass was cooled to room temperature and neutralized with saturated sodium bicarbonate solution . ir ( kbr , v  cm ) : 3385 ( nh2 ) , 3116 ( oh ) , 1600 ( c = n ) , 1217 ( c  f ) . h nmr ( 400 mhz , dmso - d6 ,   ppm ) : 6.93 ( s , 2h , nh2 ) , 7.137.77 ( m , 10h , ar c h n analysis ; calculated for c20h13f2n3o2 : c , 65.75 ; h , 3.59 ; n , 11.50 . synthesis of 4,4-difluoro-4-(5-aryl-1,3,4-oxadiazol-2-yl)-1,1:3,1-terphenyl-5-ol ( 9a  c ) a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and aromatic carboxylic acid ( 0.015  mol ) in phosphorus oxychloride ( 10  ml ) was refluxed for 8  h. the excess phosphorus oxychloride was evaporated and the cooled reaction mass was then poured into ice cold water with stirring . the separated solid was filtered and washed with saturated sodium bicarbonate solution and then with water . a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and aromatic carboxylic acid ( 0.015  mol ) in phosphorus oxychloride ( 10  ml ) was refluxed for 8  h. the excess phosphorus oxychloride was evaporated and the cooled reaction mass was then poured into ice cold water with stirring . the separated solid was filtered and washed with saturated sodium bicarbonate solution and then with water . ir ( kbr , v  cm ) : 3042 ( oh ) , 2956 ( ch ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.64 ( s , 3h , ch3 ) , 6.957.73 ( m , 14h , ar c h n analysis ; calculated for c27h18f2n2o3 : c , 71.05 ; h , 3.97 ; n , 6.14 . found : c , 71.03 ; h , 3.98 ; n , 6.12 . 
   yield 61% ; m.p 198201c . ir ( kbr , v  cm ) : 3042 ( oh ) , 2956 ( ch ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.64 ( s , 3h , ch3 ) , 6.957.73 ( m , 14h , ar c h n analysis ; calculated for c27h18f2n2o3 : c , 71.05 ; h , 3.97 ; n , 6.14 . found : c , 71.03 ; h , 3.98 ; n , 6.12 . 
 4,4-difluoro-4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1:3,1-terphenyl-5-ol ( 9b ) yield 66% ; m.p 190193c . ir ( kbr , v  cm ) : 3032 ( oh ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.987.70 ( m , 14h , ar h ) , 9.85 ( s , 1h , oh ) . lcms : m / z 445.1 ( m+1 ) . c h n analysis ; calculated for c26h15f3n2o2 : c , 70.27 ; h , 3.40 ; n , 6.30 . found : c , 70.25 ; h , 3.42 ; n , 6.28 . 
   yield 66% ; m.p 190193c . ir ( kbr , v  cm ) : 3032 ( oh ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.987.70 ( m , 14h , ar h ) , 9.85 ( s , 1h , oh ) . lcms : m / z 445.1 ( m+1 ) . c h n analysis ; calculated for c26h15f3n2o2 : c , 70.27 ; h , 3.40 ; n , 6.30 . found : c , 70.25 ; h , 3.42 ; n , 6.28 . 
 4,4-difluoro-4-[5-(biphenyl-4-yl)-1,3,4-oxadiazol-2-yl]-1,1:3,1-terphenyl-5-ol ( 9c ) yield 68% ; m.p 210213c . ir ( kbr , v  cm ) : 3039 ( oh ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.138.11 ( m , 19h , ar h ) , 10.13 ( s , 1h , oh ) . lcms : m / z 503.1 ( m+1 ) . c h n analysis ; calculated for c32h20f2n2o2 : c , 76.48 ; h , 4.01 ; n , 5.57 . ir ( kbr , v  cm ) : 3039 ( oh ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.138.11 ( m , 19h , ar h ) , 10.13 ( s , 1h , oh ) . lcms : m / z 503.1 ( m+1 ) . c h n analysis ; calculated for c32h20f2n2o2 : c , 76.48 ; h , 4.01 ; n , 5.57 . found : c , 76.44 ; h , 4.02 ; n , 5.55 . 
 synthesis of schiff base derivatives ( 10a  c ) a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and aromatic aldehyde ( 0.01  mol ) in absolute ethanol ( 25  ml ) was heated under reflux for 4  h in presence of concentrated hcl ( 0.5  ml ) . a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) and aromatic aldehyde ( 0.01  mol ) in absolute ethanol ( 25  ml ) was heated under reflux for 4  h in presence of concentrated hcl ( 0.5  ml ) . ir ( kbr , v  cm ) : 3336 ( nh ) , 3056 ( oh ) , 1637 ( c = o ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.21 ( s , 3h , och3 ) , 6.937.81 ( m , 14h , ar h ) , 8.23 ( s , 1h , ch ) , 10.32 ( s , 1h , oh ) , 11.48 ( s , 1h , nh ) . lcms : m / z 459.1 ( m ) . c h n analysis ; calculated for c27h20f2n2o3 : c , 70.73 ; h , 4.40 ; n , 6.11 . found : c , 70.71 ; h , 4.39 ; n , 6.08 . 
   yield 84% ; m.p 177180c . ir ( kbr , v  cm ) : 3336 ( nh ) , 3056 ( oh ) , 1637 ( c = o ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.21 ( s , 3h , och3 ) , 6.937.81 ( m , 14h , ar h ) , 8.23 ( s , 1h , ch ) , 10.32 ( s , 1h , oh ) , 11.48 ( s , 1h , nh ) . lcms : m / z 459.1 ( m ) . c h n analysis ; calculated for c27h20f2n2o3 : c , 70.73 ; h , 4.40 ; n , 6.11 . found : c , 70.71 ; h , 4.39 ; n , 6.08 . ir ( kbr , v  cm ) : 3354 ( nh ) , 3046 ( oh ) , 1640 ( c = o ) , 1600 ( c = n ) , 1223 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.917.78 ( m , 14h , ar h ) , 7.93 ( s , 1h , ch ) , 9.85 ( s , 1h , oh ) , 10.91 ( s , 1h , nh ) . lcms : m / z 447.1 ( m ) . c h n analysis ; calculated for c26h17f3n2o2 : c , 69.95 ; h , 3.84 ; n , 6.28 . found : c , 69.94 ; h , 3.86 ; n , 6.24 . ir ( kbr , v  cm ) : 3354 ( nh ) , 3046 ( oh ) , 1640 ( c = o ) , 1600 ( c = n ) , 1223 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.917.78 ( m , 14h , ar h ) , 7.93 ( s , 1h , ch ) , 9.85 ( s , 1h , oh ) , 10.91 ( s , 1h , nh ) . lcms : m / z 447.1 ( m ) . c h n analysis ; calculated for c26h17f3n2o2 : c , 69.95 ; h , 3.84 ; n , 6.28 . ir ( kbr , v  cm ) : 3329 ( nh ) , 3059 ( oh ) , 1647 ( c = o ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.077.97 ( m , 19h , ar h ) , 8.15 ( s , 1h , ch ) , 10.15 ( s , 1h , oh ) , 11.71 ( s , 1h , nh ) . c h n analysis ; calculated for c32h22f2n2o2 : c , 76.18 ; h , 4.40 ; n , 5.55 . found : c , 76.14 ; h , 4.38 ; n , 5.52 . 
   yield 82% ; m.p 226228c . ir ( kbr , v  cm ) : 3329 ( nh ) , 3059 ( oh ) , 1647 ( c = o ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.077.97 ( m , 19h , ar h ) , 8.15 ( s , 1h , ch ) , 10.15 ( s , 1h , oh ) , 11.71 ( s , 1h , nh ) . lcms : m / z 505.1 ( m+1 ) . c h n analysis ; calculated for c32h22f2n2o2 : c , 76.18 ; h , 4.40 ; n , 5.55 . found : c , 76.14 ; h , 4.38 ; n , 5.52 . acetylation of schiff base derivatives ( 11a  c ) a mixture of schiff base ( 0.01  mol ) and acetic anhydride ( 10  ml ) was dissolved in ethanol ( 25  ml ) and the reaction mixture was refluxed for 6  h. the reaction mixture was then concentrated and allowed to cool . the solid product obtained was filtered , washed with water , and recrystallized using ethanol - dimethyl formamide mixture . a mixture of schiff base ( 0.01  mol ) and acetic anhydride ( 10  ml ) was dissolved in ethanol ( 25  ml ) and the reaction mixture was refluxed for 6  h. the reaction mixture was then concentrated and allowed to cool . the solid product obtained was filtered , washed with water , and recrystallized using ethanol - dimethyl formamide mixture . ir ( kbr , v  cm ) : 3059 ( oh ) , 2933 , 2837 ( ch ) , 1770 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.84 ( s , 3h , coch3 ) , 3.45 ( s , 3h , och3 ) , 6.41 ( s , 1h , ch ) , 6.747.85 ( m , 14h , ar h ) , 9.98 ( s , 1h , oh ) . lcms : m / z 501.1 ( m+1 ) . c h n analysis ; calculated for c29h22f2n2o4 : c , 69.59 ; h , 4.43 ; n , 5.60 . found : c , 69.57 ; h , 4.44 ; n , 5.58 . ir ( kbr , v  cm ) : 3059 ( oh ) , 2933 , 2837 ( ch ) , 1770 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.84 ( s , 3h , coch3 ) , 3.45 ( s , 3h , och3 ) , 6.41 ( s , 1h , ch ) , 6.747.85 ( m , 14h , ar h ) , 9.98 ( s , 1h , oh ) . lcms : m / z 501.1 ( m+1 ) . c h n analysis ; calculated for c29h22f2n2o4 : c , 69.59 ; h , 4.43 ; n , 5.60 . found : c , 69.57 ; h , 4.44 ; n , 5.58 . 
 1-[5-(4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)-2-(4-fluorophenyl)-1,3,4-oxadiazol-3(2h)-yl]ethanone ( 11b ) yield 45% ; m.p 142145c . ir ( kbr , v  cm ) : 3043 ( oh ) , 2889 ( ch ) , 1762 ( c = o ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.72 ( s , 3h , coch3 ) , 6.52 ( s , 1h , ch ) , 6.827.91 ( m , 14h , ar h ) , 9.85 ( s , 1h , oh ) . lcms : m / z 489.1 ( m ) . c h n analysis ; calculated for c28h19f3n2o3 : c , 68.85 ; h , 3.92 ; n , 5.74 . found : c , 68.83 ; h , 3.90 ; n , 5.73 . 
   yield 45% ; m.p 142145c . ir ( kbr , v  cm ) : 3043 ( oh ) , 2889 ( ch ) , 1762 ( c = o ) , 1604 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.72 ( s , 3h , coch3 ) , 6.52 ( s , 1h , ch ) , 6.827.91 ( m , 14h , ar h ) , 9.85 ( s , 1h , oh ) . lcms : m / z 489.1 ( m ) . c h n analysis ; calculated for c28h19f3n2o3 : c , 68.85 ; h , 3.92 ; n , 5.74 . found : c , 68.83 ; h , 3.90 ; n , 5.73 . ir ( kbr , v  cm ) : 3032 ( oh ) , 2915 ( ch ) , 1742 ( c = o ) , 1611 ( c = n ) , 1215 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.94 ( s , 3h , coch3 ) , 6.48 ( s , 1h , ch ) , 7.037.99 ( m , 19h , ar h ) , 10.15 ( s , 1h , oh ) . lcms : m / z 547.1 ( m ) . c h n analysis ; calculated for c34h24f2n2o3 : c , 74.71 ; h , 4.43 ; n , 5.13 . found : c , 74.72 ; h , 4.42 ; n , 5.10 . 
   yield 50% ; m.p 133126c . ir ( kbr , v  cm ) : 3032 ( oh ) , 2915 ( ch ) , 1742 ( c = o ) , 1611 ( c = n ) , 1215 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.94 ( s , 3h , coch3 ) , 6.48 ( s , 1h , ch ) , 7.037.99 ( m , 19h , ar h ) , 10.15 ( s , 1h , oh ) . lcms : m / z 547.1 ( m ) . c h n analysis ; calculated for c34h24f2n2o3 : c , 74.71 ; h , 4.43 ; n , 5.13 . synthesis of 5-(4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)-1,3,4-oxadiazole-2(3h)-thione ( 12 ) to a solution of carbohydrazide 4 ( 3.4  g , 0.01  mol ) in ethanol ( 10  ml ) a solution of carbon disulphide ( 1.14  g , 0.015  mol ) in water ( 3  ml ) and potassium hydroxide ( 1  g ) was added , and the mixture was refluxed until the evolution of h2s ceased ( 7 - 8  h ) . the solid obtained was collected by filtration , washed with least amount of water , and recrystallized from ethanol - water ( 1  :  1 ) . ir ( kbr , v  cm ) : 3224 ( nh ) , 3124 ( oh ) , h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.177.78 ( m , 10h , ar h ) , 10.75 ( s , 1h , oh ) , 14.53 ( s , 1h , nh ) . lcms : m / z 383.0 ( m+1 ) . c h n analysis ; calculated for c20h12f2n2o2s : c , 62.82 ; h , 3.16 ; n , 7.33 . found : c , 62.80 ; h , 3.17 ; n , 7.30 . 
   to a solution of carbohydrazide 4 ( 3.4  g , 0.01  mol ) in ethanol ( 10  ml ) a solution of carbon disulphide ( 1.14  g , 0.015  mol ) in water ( 3  ml ) and potassium hydroxide ( 1  g ) was added , and the mixture was refluxed until the evolution of h2s ceased ( 7 - 8  h ) . the solid obtained was collected by filtration , washed with least amount of water , and recrystallized from ethanol - water ( 1  :  1 ) . ir ( kbr , v  cm ) : 3224 ( nh ) , 3124 ( oh ) , h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 7.177.78 ( m , 10h , ar h ) , 10.75 ( s , 1h , oh ) , 14.53 ( s , 1h , nh ) . lcms : m / z 383.0 ( m+1 ) . c h n analysis ; calculated for c20h12f2n2o2s : c , 62.82 ; h , 3.16 ; n , 7.33 . . 
 synthesis of 4-amino-5-(4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)-2,4-dihydro-3h-1,2,4-triazole-3-thione ( 13 ) a mixture of the oxadiazole 12 ( 3.82  g , 0.01  mol ) and hydrazine hydrate ( 5  ml , 95% ) in water ( 20  ml ) was refluxed with stirring for 4  h , diluted with cold water ( 200  ml ) , acidified by the drop wise addition of concentrated hydrochloric acid , and filtered off . the solid formed was washed with the least amount of cold water and recrystallized from ethanol - dimethyl formamide mixture . ir ( kbr , v  cm ) : 3373 ( nh2 ) , 3259 ( nh ) , 3163 ( oh ) , 1616 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 5.45 ( s , 2h , nh2 ) , 7.117.76 ( m , 10h , ar h ) , 10.43 ( s , 1h , oh ) , 13.54 ( s , 1h , nh ) . lcms : m / z 397.0 ( m+1 ) . c h n analysis ; calculated for c20h14f2n4os : c , 60.60 ; h , 3.56 ; n , 14.13 . found : c , 60.56 ; h , 3.57 ; n , 14.10 . 
   a mixture of the oxadiazole 12 ( 3.82  g , 0.01  mol ) and hydrazine hydrate ( 5  ml , 95% ) in water ( 20  ml ) was refluxed with stirring for 4  h , diluted with cold water ( 200  ml ) , acidified by the drop wise addition of concentrated hydrochloric acid , and filtered off . the solid formed was washed with the least amount of cold water and recrystallized from ethanol - dimethyl formamide mixture . ir ( kbr , v  cm ) : 3373 ( nh2 ) , 3259 ( nh ) , 3163 ( oh ) , 1616 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 5.45 ( s , 2h , nh2 ) , 7.117.76 ( m , 10h , ar h ) , 10.43 ( s , 1h , oh ) , 13.54 ( s , 1h , nh ) . lcms : m / z 397.0 ( m+1 ) . c h n analysis ; calculated for c20h14f2n4os : c , 60.60 ; h , 3.56 ; n , 14.13 . found : c , 60.56 ; h , 3.57 ; n , 14.10 . 
 synthesis of mannich bases ( 14a  c ) to a solution of oxadiazole 12 ( 3.82  g , 0.01 mole ) in ethanol ( 5  ml ) , formaldehyde ( 0.5  ml , 37% ) and secondary amine ( 0.01  mol ) were added . after cooling , the precipitate was filtered and recrystallized from ethanol . 
   to a solution of oxadiazole 12 ( 3.82  g , 0.01 mole ) in ethanol ( 5  ml ) , formaldehyde ( 0.5  ml , 37% ) and secondary amine ( 0.01  mol ) were added . ir ( kbr , v  cm ) : 3157 ( oh ) , 2937 , 2858 ( ch ) , 1620 ( c = n ) , 1236 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.35 ( t , 4h , n - ch2 of morpholine ) , 3.45 ( t , 4h , o  ch2 of morpholine ) , 4.90 ( s , 2h , n c h n analysis ; calculated for c25h21f2n3o3s : c , 62.36 ; h , 4.40 ; n , 8.73 . found : c , 62.34 ; h , 4.41 ; n , 8.71 . 
   yield 72% ; m.p 200202c . ir ( kbr , v  cm ) : 3157 ( oh ) , 2937 , 2858 ( ch ) , 1620 ( c = n ) , 1236 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.35 ( t , 4h , n - ch2 of morpholine ) , 3.45 ( t , 4h , o  ch2 of morpholine ) , 4.90 ( s , 2h , n c h n analysis ; calculated for c25h21f2n3o3s : c , 62.36 ; h , 4.40 ; n , 8.73 . ir ( kbr , v  cm ) : 3163 ( oh ) , 2862 ( ch ) , 1616 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.29 ( s , 3h , n ch3 ) , 2.45 ( t , 2h , ch2 ) , 2.95 ( t , 4h , ch2 ) , 5.07 ( s , 2h , n c h n analysis ; calculated for c26h24f2n4o2s : c , 63.14 ; h , 4.89 ; n , 11.33 . found : c , 63.12 ; h , 4.87 ; n , 11.30 . ir ( kbr , v  cm ) : 3163 ( oh ) , 2862 ( ch ) , 1616 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 2.29 ( s , 3h , n ch3 ) , 2.45 ( t , 2h , ch2 ) , 2.95 ( t , 4h , ch2 ) , 5.07 ( s , 2h , n c h n analysis ; calculated for c26h24f2n4o2s : c , 63.14 ; h , 4.89 ; n , 11.33 . found : c , 63.12 ; h , 4.87 ; n , 11.30 . ir ( kbr , v  cm ) : 3173 ( oh ) , 2912 ( ch ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.551.61 ( m , 6h , ch2 ) , 2.82 ( t , 4h , n c h n analysis ; calculated for c26h23f2n3o2s : c , 65.12 ; h , 4.83 ; n , 8.76 . found : c , 65.10 ; h , 4.84 ; n , 8.74 . 
   yield 61% ; m.p 98100c . ir ( kbr , v  cm ) : 3173 ( oh ) , 2912 ( ch ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.551.61 ( m , 6h , ch2 ) , 2.82 ( t , 4h , n c h n analysis ; calculated for c26h23f2n3o2s : c , 65.12 ; h , 4.83 ; n , 8.76 . alkylation of 1,3,4-oxadiazole-2-thione derivative ( 15a  c ) oxadiazole 12 ( 3.82  g , 0.01  mol ) was dissolved in ethanol ( 20  ml ) and 10% aqueous sodium hydroxide solution ( 3.5  ml ) was added . alkyl halide ( 0.02  mol ) was added and heated to reflux for 4  h. the reaction mixture was then poured into ice cold water , filtered , and crystallized from ethanol . oxadiazole 12 ( 3.82  g , 0.01  mol ) was dissolved in ethanol ( 20  ml ) and 10% aqueous sodium hydroxide solution ( 3.5  ml ) was added . alkyl halide ( 0.02  mol ) was added and heated to reflux for 4  h. the reaction mixture was then poured into ice cold water , filtered , and crystallized from ethanol . ir ( kbr , v  cm ) : 2964 ( ch ) , 1560(c = n ) , 1170 ( c  f ) . c h n analysis ; calculated for c28h28f2n2o2s : c , 67.99 ; h , 5.71 ; n , 5.66 . found : c , 67.96 ; h , 5.69 ; n , 5.63 . 
   yield 63% ; m.p 270272c . ir ( kbr , v  cm ) : 2964 ( ch ) , 1560(c = n ) , 1170 ( c  f ) . c h n analysis ; calculated for c28h28f2n2o2s : c , 67.99 ; h , 5.71 ; n , 5.66 . ir ( kbr , v  cm ) : 2972 ( ch ) , 1572(c = n ) , 1220 ( c  f ) . c h n analysis ; calculated for c24h20f2n2o2s : c , 65.74 ; h , 4.60 ; n , 6.39 . found : c , 65.71 ; h , 4.57 ; n , 6.35 . 
   yield 58% ; m.p 222224c . ir ( kbr , v  cm ) : 2972 ( ch ) , 1572(c = n ) , 1220 ( c  f ) . c h n analysis ; calculated for c24h20f2n2o2s : c , 65.74 ; h , 4.60 ; n , 6.39 . ir ( kbr , v  cm ) : 2954 ( ch ) , 1724 ( c = o ester ) , 1220 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.14 ( m , 6h , 2  ch3 ) , 3.34 ( s , 2h , sch2 ) , 4.09 ( m , 4h , 2  ch2 ) , 5.05 ( s , 2h , och2 ) , 7.167.91 ( m , 10h , ar  h ) . c h n analysis ; calculated for c28h24f2n2o6s : c , 60.64 ; h , 4.36 ; n , 5.05 . ir ( kbr , v  cm ) : 2954 ( ch ) , 1724 ( c = o ester ) , 1220 ( c  f ) . h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 1.14 ( m , 6h , 2  ch3 ) , 3.34 ( s , 2h , sch2 ) , 4.09 ( m , 4h , 2  ch2 ) , 5.05 ( s , 2h , och2 ) , 7.167.91 ( m , 10h , ar  h ) . c h n analysis ; calculated for c28h24f2n2o6s : c , 60.64 ; h , 4.36 ; n , 5.05 . synthesis of 2-[(4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-yl)carbonyl]hydrazine carbothioamide ( 16)a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) , potassium thiocyanate ( 0.015  mol ) , and hydrochloric acid ( 5  ml ) in water ( 25  ml ) was refluxed for 4  h with stirring . the resulting solid that separated was washed with hot water and recrystallized from 75% ethanol . ir ( kbr , v  cm ) : 3464 , 3329 ( nh ) , 3236 ( oh ) , 1672 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.96 , 8.19 ( two singlets , 2h , nh2 ) , 7.097.71 ( m , 10h , ar h ) , 9.57 ( s , 1h , nh ) , 10.45 ( s , 1h , nh ) , 10.75 ( s , 1h , oh ) . lcms : m / z 400.0 ( m+1 ) . c h n analysis ; calculated for c20h15f2n3o2s : c , 60.14 ; h , 3.79 ; n , 10.52 . a mixture of carbohydrazide 4 ( 3.4  g , 0.01  mol ) , potassium thiocyanate ( 0.015  mol ) , and hydrochloric acid ( 5  ml ) in water ( 25  ml ) was refluxed for 4  h with stirring . the resulting solid that separated was washed with hot water and recrystallized from 75% ethanol . ir ( kbr , v  cm ) : 3464 , 3329 ( nh ) , 3236 ( oh ) , 1672 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.96 , 8.19 ( two singlets , 2h , nh2 ) , 7.097.71 ( m , 10h , ar h ) , 9.57 ( s , 1h , nh ) , 10.45 ( s , 1h , nh ) , 10.75 ( s , 1h , oh ) . lcms : m / z 400.0 ( m+1 ) . c h n analysis ; calculated for c20h15f2n3o2s : c , 60.14 ; h , 3.79 ; n , 10.52 . . 
 synthesis of 1,3-thiazol derivatives ( 17a  c ) an equimolar mixture of thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) and phenacyl bromide derivative ( 0.001  mol ) in 20  ml of absolute ethanol was heated under reflux for 4  h. the product that separated after cooling was collected and recrystallized from ethanol . an equimolar mixture of thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) and phenacyl bromide derivative ( 0.001  mol ) in 20  ml of absolute ethanol was heated under reflux for 4  h. the product that separated after cooling was collected and recrystallized from ethanol . ir ( kbr , v  cm ) : 3331(nh ) , 3196 ( oh ) , 1654 ( c = o ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.75 ( s , 3h , och3 ) , 6.917.73 ( m , 14h , ar h ) , 9.47 ( s , 1h , nh ) , 10.23 ( s , 1h , nh ) , 10.37 ( s , 1h , oh ) . lcms : m / z 530.1 ( m+1 ) . c h n analysis ; calculated for c29h21f2n3o3s : c , 65.77 ; h , 4.00 ; n , 7.93 . found : c , 65.74 ; h , 3.96 ; n , 7.90 . 
   yield 64% ; m.p 213215c . ir ( kbr , v  cm ) : 3331(nh ) , 3196 ( oh ) , 1654 ( c = o ) , 1606 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.75 ( s , 3h , och3 ) , 6.917.73 ( m , 14h , ar h ) , 9.47 ( s , 1h , nh ) , 10.23 ( s , 1h , nh ) , 10.37 ( s , 1h , oh ) . lcms : m / z 530.1 ( m+1 ) . c h n analysis ; calculated for c29h21f2n3o3s : c , 65.77 ; h , 4.00 ; n , 7.93 . ir ( kbr , v  cm ) : 3329 ( nh ) , 3236 ( oh ) , 1662 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.817.67 ( m , 14h , ar h ) , 9.39 ( s , 1h , nh ) , 10.17 ( s , 1h , nh ) , 10.41 ( s , 1h , oh ) . lcms : m / z 518.2 ( m+1 ) . c h n analysis ; calculated for c28h18f3n3o2s : c , 64.98 ; h , 3.51 ; n , 8.12 . found : c , 64.96 ; h , 3.50 ; n , 8.08 . 
   yield 67% ; m.p 200202c . ir ( kbr , v  cm ) : 3329 ( nh ) , 3236 ( oh ) , 1662 ( c = o ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.817.67 ( m , 14h , ar h ) , 9.39 ( s , 1h , nh ) , 10.17 ( s , 1h , nh ) , 10.41 ( s , 1h , oh ) . lcms : m / z 518.2 ( m+1 ) . c h n analysis ; calculated for c28h18f3n3o2s : c , 64.98 ; h , 3.51 ; n , 8.12 . ir ( kbr , v  cm ) : 3324 ( nh ) , 3214 ( oh ) , 1652 ( c = o ) , 1601 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.698.14 ( m , 19h , ar h ) , 9.41 ( s , 1h , nh ) , 10.29 ( s , 1h , nh ) , 10.74 ( s , 1h , oh ) . lcms : m / z 576.3 ( m+1 ) . c h n analysis ; calculated for c34h23f2n3o2s : c , 70.94 ; h , 4.03 ; n , 7.30 . found : c , 70.91 ; h , 4.01 ; n , 7.27 . 
   yield 60% ; m.p 169172c . ir ( kbr , v  cm ) : 3324 ( nh ) , 3214 ( oh ) , 1652 ( c = o ) , 1601 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 6.698.14 ( m , 19h , ar h ) , 9.41 ( s , 1h , nh ) , 10.29 ( s , 1h , nh ) , 10.74 ( s , 1h , oh ) . lcms : m / z 576.3 ( m+1 ) . c h n analysis ; calculated for c34h23f2n3o2s : c , 70.94 ; h , 4.03 ; n , 7.30 . . 
 synthesis of 4,4-difluoro-4-(5-sulfanyl-4h-1,2,4-triazol-3-yl)-1,1:3,1-terphenyl-5-ol ( 18 ) a suspension of the thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) in sodium hydroxide solution ( 10  ml , 10% ) was heated under reflux for 10  h. the reaction mixture was allowed to cool and then adjusted to ph 6 with 10% hydrochloric acid . the precipitate that formed was filtered off , washed with water , dried , and recrystallized from ethanol . ir ( kbr , v  cm ) : 3433 , 3329 ( nh ) , 3236 ( oh ) , 2372 ( sh ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 4.07 ( s , 1h , sh ) , 7.057.72 ( m , 10h , ar h ) , 10.23 ( s , 1h , oh ) , 13.54 ( s , 1h , nh ) . lcms : m / z 382.0 ( m+1 ) . c h n analysis ; calculated for c20h13f2n3os : c , 62.98 ; h , 3.44 ; n , 11.02 . a suspension of the thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) in sodium hydroxide solution ( 10  ml , 10% ) was heated under reflux for 10  h. the reaction mixture was allowed to cool and then adjusted to ph 6 with 10% hydrochloric acid . the precipitate that formed was filtered off , washed with water , dried , and recrystallized from ethanol . ir ( kbr , v  cm ) : 3433 , 3329 ( nh ) , 3236 ( oh ) , 2372 ( sh ) , 1608 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 4.07 ( s , 1h , sh ) , 7.057.72 ( m , 10h , ar h ) , 10.23 ( s , 1h , oh ) , 13.54 ( s , 1h , nh ) . lcms : m / z 382.0 ( m+1 ) . c h n analysis ; calculated for c20h13f2n3os : c , 62.98 ; h , 3.44 ; n , 11.02 . synthesis of 4,4-difluoro-5-hydroxy - n-(5-oxo-2-sulfanyl-4,5-dihydro-1h - imidazol-1-yl)-1,1:3,1-terphenyl-4-carboxamide ( 19 ) a mixture of thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) , monochloroacetic acid ( 0.001  mol ) , and anhydrous sodium acetate ( 0.002  mol ) in glacial acetic acid ( 30  ml ) was refluxed for 8  h. after cooling , the reaction mixture was poured on crushed ice . ir ( kbr , v  cm ) : 3327 ( nh ) , 3132 ( oh ) , 1724 , 1635 ( c = o ) , 1598 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.88 ( s , 2h , ch2 ) , 4.10 ( s , 1h , sh ) , 6.947.78 ( m , 10h , ar h ) , 10.59 ( s , 1h , nh ) , 10.60 ( s , 1h , oh ) . lcms : m / z 440.0 ( m+1 ) . c h n analysis ; calculated for c22h15f2n3o3s : c , 60.13 ; h , 3.44 ; n , 9.56 . a mixture of thiosemicarbazide derivative 16 ( 0.399  g , 0.001  mol ) , monochloroacetic acid ( 0.001  mol ) , and anhydrous sodium acetate ( 0.002  mol ) in glacial acetic acid ( 30  ml ) was refluxed for 8  h. after cooling , the reaction mixture was poured on crushed ice . ir ( kbr , v  cm ) : 3327 ( nh ) , 3132 ( oh ) , 1724 , 1635 ( c = o ) , 1598 ( c = h nmr ( 400  mhz , dmso - d6 ,   ppm ) : 3.88 ( s , 2h , ch2 ) , 4.10 ( s , 1h , sh ) , 6.947.78 ( m , 10h , ar h ) , 10.59 ( s , 1h , nh ) , 10.60 ( s , 1h , oh ) . lcms : m / z 440.0 ( m+1 ) . c h n analysis ; calculated for c22h15f2n3o3s : c , 60.13 ; h , 3.44 ; n , 9.56 . the newly synthesized compounds were screened for their antibacterial activity against escherichia coli ( attc-25922 ) , staphylococcus aureus ( attc-25923 ) , pseudomonas aeruginosa ( atcc-27853 ) , and klebsiella pneumoniae ( recultured ) bacterial strains by serial plate dilution method . serial dilutions of the drug in mueller - hinton broth were taken in tubes and their ph was adjusted to 5.0 using phosphate buffer . a standardized suspension of the test bacterium was inoculated and incubated for 1618  h at 37c . the minimum inhibitory concentration ( mic ) was noted by seeing the lowest concentration of the drug at which there was no visible growth . a number of antimicrobial discs were placed on the agar for the sole purpose of producing zones of inhibition in the bacterial lawn . excess of suspension was decanted and plates were dried by placing in an incubator at 37c for an hour . using a punch , wells were made on these seeded agar plates and minimum inhibitory concentrations of the test compounds in dimethylsulfoxide ( dmso ) were added into each labeled well . a control was also prepared for the plates in the same way using solvent dmso . the petri dishes were prepared in triplicate and maintained at 37c for 3 - 4 days . zone of inhibition was determined for newly synthesized compounds and the results are summarized in table 1 . newly prepared compounds were screened for their antifungal activity against aspergillus flavus ( ncim no . 902 ) , penicillium ( s. aureus ) ( recultured ) , and trichophyton mentagrophytes ( recultured ) in dmso by serial plate dilution method . sabourands agar media were prepared by dissolving peptone ( 1  g ) , d - glucose ( 4  g ) and agar ( 2  g ) in distilled water ( 100  ml ) and adjusting the ph to 5.7 . normal saline was used to make a suspension of spore of fungal strains for lawning . a loopful of particular fungal strain was transferred to 3  ml saline to get a suspension of corresponding species . excess of suspension were decanted and plates were dried by placing in incubator at 37c for 1  h. using a punch , wells were made on these seeded agar plates minimum inhibitory concentrations of the test compounds in dmso were added into each labeled well . a control was also prepared for the plates in the same way using solvent dmso . the petri dishes were prepared in triplicate and maintained at 37c for 3 - 4 days . zones of inhibition were determined and the results are summarized in table 2 . the dpph assay was based on the reported method . briefly , 1  mm solution of dpph in ethanol was prepared , and this solution ( 1  ml ) was added to sample solutions 1  mg / ml of dmso . the mixture was shaken vigorously and allowed to stand at room temperature for 20  min the capability to scavenge the dpph radical was calculated using the following equation : 
 ( 1)dpph  scavenging  effect  ( % ) = ( a0a1a0)100 , 
 where a0 is the absorbance of the control reaction and a1 is the absorbance in the presence of the samples or standards . each sample was assayed at 1  mg / ml and all experiments were carried out in triplicate and the % rsc is shown in table 3 . the reducing power of the synthesized compounds was determined according to the method of oyaizu . different concentrations of the samples ( 1001000  g / ml ) in dmso ( 1  ml ) were mixed with phosphate buffer ( 2.5  ml , 0.2  m , ph = 6.6 ) and potassium ferricyanide ( 2.5  ml , 1% solution ) . after which 10% trichloroacetic acid ( 2.5  ml ) was added to the mixture , which was then centrifuged for 10  min . the upper layer of solution ( 2.5  ml ) was mixed with distilled water ( 2.5  ml ) and fecl3 ( 0.5  ml , 0.1% ) and then the absorbance at 700  nm was measured using a spectrophotometer . all experiments were carried out in triplicate and the reducing power assay was represented by effective concentration ( mg / ml ) equivalent to 0.5 absorbance glutathione ( table 3 ) .
new functionalized terphenyl derivatives incorporating various heterocyclic rings are prepared by using 4,4-difluoro-5-hydroxy-1,1:3,1-terphenyl-4-carbohydrazide as a key intermediate derived from 4,4-difluoro chalcone , a versatile synthone . 
 all the derivatives are characterized by 1h nmr , ir , and mass spectral data . 
 all the synthesized products are screened for their in vitro antimicrobial and antioxidant properties . 
 the majority of the tested compounds exhibited significant antioxidant activity and some of them showed good antimicrobial activity .