Synthesis, Characterization and Biological Study of Some Chalcones derived from Terphthaldehyde

 

Suha K. Al-Mosawi¹, Hanan A. Al-Hazam², Abbas F. Abbas²

¹Department of Pharmaceutical Chemistry, College of Pharmacy, University of Basrah, Basrah-Iraq

²Department of Chemistry, College of Science, University of Basrah, Basrah-Iraq

*CorrespondingAuthorE-mail:almosowi.suha80@gmail.com

 

 

INTRODUCTION:

Schiff base compounds have been shown to be promising leads for the design of efficient antimicrobial agents as a result of the broad range of biological activities exhibited by these compounds. These compounds are reported to exhibit antifungal, antibacterial, antimalarial, antiproliferative, anti-inflammatory, antiviral and antipyretic properties [1-3]. The mode of interaction and inhibition effectiveness of Schiff bases with bacteria and fungi is expected to depend on the molecular structure of the compounds. Thus, advances in this field will require analyses of structureactivity relationships of Schiff bases along with investigation of the mechanism of action of these compounds [4]. In particular, Schiff bases composed of terphthaldehyde are very promising in the search of new functional materials. They exhibit a variety of biological activities [5-7] as well as show important photochromism where light absorption causes interconversion between enolimine and keto-amine tautomers through intramolecular hydrogen transfer.

 

As part of our efforts to study structure activity relationship of Schiff bases, we report the effect of substituent position on the electronic spectra and antimicrobial activity of Schiff bases of isomeric 4-amino acetophenone with terphthaldehyde.

 

EXPERIMENTAL:

1. MATERIAL AND METHODS:

All chemicals were obtained commercially from Sigma Aldrich Chemicals. The solvents: ethanol, N,N”-dimethylformamide (DMF) and acetonitrile were of spectroscopic grade and used without further purification. Infrared spectra were recorded as KBr pellets on a Shimadzu FT-IR 8400 affinity Spectrophotometer. ¹H NMR Spectra were obtained using a Varian 500 MHz spectrometer (DMSO-d6) solution with tetramethylsilane (TMS) as internal standard. Microanalytically data were determined using a CE-440 Elemental analyzer, EAI Exeter Analytical Inc. Melting points were determined with Gallenkamp melting point apparatus.

 

2. Synthesis of a Schiff Base (T):

Ethanollic mixture of terphthaldehyde (0.134 gm, 0.001mole) with 4-amino acetophenone (0.135gm, 0.002mole) were reflexed at 65^oC in presence of ethanol 20 ml with addition three drops of glacial acetic acid. The reaction was monitored by thin layer chromatography (TLC) by using eluent acetone: chloroform (2:8) respectively. The solvent was evaporated and yellow precipitation was recrystallized from absolute ethanol to give compound (T) dark yellow, Yield 60%, M.P 199-200^oC.

 

3. Synthesis of Schiff Base Chalcone Compounds (E1-E10):

Stirred mixture of (0.02mole) Benzaldehyde derivatives and (0.386 gm, 0.001mole) from (T) compound in 25ml DMF then added 5ml from sodium hydroxide (40%) and kept overnight at room temperature; the mixture was poured into crashed ice and acidified with 10% HCl. The solid separated was filtered and recrystallized from absolute ethanol. The products were obtained in 53-68%.

RESULT AND DISCUSSION:

The Schiff base Chalcone compounds (E1-E10) were prepared by the condensation reaction of terphthaldehyde with the corresponding 4-amino acetophenone as illustrated in Scheme 1 below. (E1-E10) differed only in the position of the functional group on the phenyl ring. The compounds are soluble in organic solvents such as DMF, DMSO and dioxane but insoluble in hexane and toluene. The physical and analytical data are presented in Table 1, 2 and 3 Important IR[8-10], ¹HNMR[11-14] and ¹³CNMR[15,16] peaks for the compounds are listed in Table 2.

 

Table (1): Some Physical Data of Schiff Base Chalcone Compounds

Symbol of Schiff base chalcone	Name of Schiff base chalcone	Colour	Melting Point (0C)	Yield (%)	Rf
E1 (4-Br)	Bis benzilidine bis 3-(4-bromophenyl)propane 2-en-1-one	Deep yellow	239-241	69	0.77
E2 (4-CH3)	Bis benzilidine bis 3-(4-phenyl)propane 2-en-1-one	Brawn yellow	193-195	63	0.63
E3 (4-Cl)	Bis benzilidine bis 3-(4-chlorophenyl)propane 2-en-1-one	Pale yellow	240-242	66	0.69
E4 (4-F)	Bis benzilidine bis 3-(4-fluorophenyl)propane 2-en-1-one	Brawn yellow	108-110	65	0.62
E5 (H)	Bis benzilidine bis 3-(4-phenyl)propane 2-en-1-one	Dark yellow	66-68	66	0.62
E6 4-N(CH3)2	Bis benzilidine bis 3-(4-N,N-dimethylphenyl)propane 2-en-1-one	Orange	158-160	63	0.70
E7 (4-NO2)	Bis benzilidine bis 3-(4-nitrophenyl)propane 2-en-1-one	yellow	97-99	76	0.62
E8 (4-OCH3)	Bis benzilidine bis 3-(4-methoxyphenyl)propane 2-en-1-one	yellow	188-190	60	0.79
E9 (4-OH)	Bis benzilidine bis 3-(4-hydroxyphenyl)propane 2-en-1-one	yellow	118-120	59	0.69
E10 (NH2)	Bis benzilidine bis 3-(4-aminophenyl)propane 2-en-1-one	Brawn	Oily	56	0.61

 

Table (2): Data of the FT-IR Spectra of Substituent Schiff Base Chalcone Compounds

Sym.	C=O Str.	C=N Ar. Str.	C=C Ar. Str.	CH Ar. Str.	CH, CH3 Al. Str.	NH2 and OH Str.	C-Hal
E1	1651s	1600s	1485m	3055w	2924	-------	813s
E2	1654s	1597s	1519s	3051w	2974w	-------
E3	1654s	1597s	1489s	3055w	2928w	-------	825s
E4	1724m	1597s	1508m		2974w	-------	825s
E5	1654s	1593s	1446m	3059w	2970w	-------	-------
E6	1670s	1577s	1520m	-------	2924w	-------	-------
E7	1678s	1618s	1577s	-------	-------	-------	-------
E8	1635s	1589s	1512s	-------	2924w	-------	-------
E9	1647m	1604s	1485m	-------	-------	3464s	-------
E10	1666s	1577s	1438m	3055w	2920	3363m, 3232w	-------

str. =stretching; Hal=Br, Cl, F; w=weak, s=strong, m=medium, Ar=Aromatic. Al=Aliphatic

 

Table (3): Chemical shift (ppm) of substituent chalcone compounds

Sym.	Ar. CH	CH=N	C=CH	OH, NH2	CH3, N(CH3)2 OCH3	DMSO-d6 and H2O
E1	7.40-8.85	6.60	6.18	-------	-------	2.50, 3.3
E2	-------	------	-------	-------	-------	-------
E3	7.48-8.31	6.18	-------	-------	-------	2.50, 3.3
E4	7.25-795	6.58	6.16	-------	-------	2.50, 3.3
E5	7.29-7.92	6.53	6.07	-------	-------	2.50, 3.3
E6	6.78-8.68	6.54	6.02	-------	3.02	2.50, 3.3
E7	6.61-8.41	6.22	6.06	-------	-------	2.50, 3.3
E8	7.39-8.75	6.82	6.71	-------	3.82	2.50, 3.3
E9	6.91-8.76	6.54	6.02	9.76	-------	2.50, 3.3
E10	7.62-8.32	6.54	6.21	9.66 and10.04	-------	2.50, 3.3

 

 

Figure (1): Numbring Carbon Atom of Schiff Base Compounds

Table (4): Chemical Shift (ppm) of Substituent Schiff Base Compounds

 

The compound of Schiff base were synthesized in this study from the reaction of (0.02mole) of 4-amino acetophenone with (0.01mole) of terphthaldehyde in the presence of glacial acetic acid as catalyst, as shown in scheme (1).

 

 

Scheme (1): Formation of Terphthaldehyde Schiff Base

 

The glacial acetic acid acts as protonation agent for the carbonyl of aldehyde moiety, resulting in enhancing the reaction rate of product. The amount of acid must be taken in account. It must be adequate only for the protonation since the excess of acid led to protonation of amine of 4- amino acetophenone and resulting in reducing its activity as nucleophile.

 

A series of terphthaldehyde Schiff bases chalcone were prepared according to Claisen Schmidt condensation of variously substituted aromatic aldehydes with (T) compound by using base catalyzed, under stirrer overnight to give corresponding chalcones depending on substituents of benzaldehyde. The reactions were monitored for their completion by TLC, as shown in scheme (2).

 

 

Scheme (2): Formation of Terphthaldehyde Schiff Base Chalcone compounds

 

The synthesized chalcones showed different yield depending on the substituent groups, as they were electron with drawing group or electron donating group. Aldehydes with electron donating groups led to increase the electron density on the carbon atom of carbonyl group, results in enhancing their electronic properties and hence decreasing yield of products. In contrasting, those with electron withdrawing groups caused in increasing yield as the electron density on carbon atom of carbonyl were decreased.as show in table (5).

 

Table (5): The Percentage Yield of Substituted Chalcone Compounds

Compounds	R	Yield (%)
E1	(4-Br)	69
E2	(4-CH3)	63
E3	(4-Cl)	66
E4	(4-F)	65
E5	(H)	66
E6	N(CH3)2	63
E7	(NO2)	76
E8	(OCH3)	60
E9	(OH)	59
E10	(NH2)	56

 

 

Biological Activity:

The antibacterial [17,18] activities of the series (E1-E10) have been carried out against some strain of bacteria. The result [Table6] showed that prepared compounds are toxic against the bacteria. The compounds (E1-E10) were found more active against the above microbes. The comparison of the antibacterial activity of these compounds with Streptomycin shows that these compounds have almost similar activity. The bacterial cultures for S. aurous and E. coli were obtained from Department of biology University of Basrah. Iraq. The bacterial cultures were incubated at 30^oC for 24 hours by inoculation into nutrient agar. chalcones were stored dry at room temperature and dissolved 20mg/ml in dimethyl sulfoxide (DMSO). Antibacterial activities of each compound were evaluated by the agar disc-diffusion method. Mueller Hinton Agar Media (15cm³) kept at 45^oC was poured in the petridishes and allowed to solidify. Poured Petri plates [9cm] were incubated with 50μL of normal saline solution of above culture media (105-106 bacteria per ml). Discs injected with prepared chalcones (50μL) were applied on the solid agar medium by pressing tightly. The Petri plates were placed at 37^oC for 24 hours. At the end of period, the inhibition zones formed on media were measured with a zone reader in millimeters.

 

Table (1): Inhibition Zones (mm) of The Synthesis Schiff base chalcone Compounds

Code	*E. Coli	*S. aureus
E1	8	13
E2	8	10
E3	10	10
E4	zero	zero
E5	10	12
E6	15	25
E7	zero	10
E8	15	20
E8	15	15
E9	30	30
E10	22	17
Streptomycin	9	9

*Staphylococcus aureus, *Escherichia coli,

 

REFERENCES:

1.      D.N. Dhar, and C.L. Taploo, (1982) Schiff bases and their applications. Journal of Scientific and Industrial Research, 41, 501-506.

2.      P., Przybylski, A., Huczynski, K., Pyta, B., Brzezinski, and F. Bartl, (2009) Biological properties of Schiff bases and azo derivatives of phenol. Current Organic Chemistry, 13, 124-148.

3.      T.M., Fasina, O., Ogundele, F.N. Ejiah, and Dueke-Eze, C.U. (2012) Biological Activity of copper (II), cobalt (II), and nickel (II) complexes of Schiff base derived from ophenylenediamine and 5-bromosalicylaldehyde. International Journal of Biological Chemistry, 6, 24-30

4.      da Silva, C.M., da Silva, D.L., Modolo, L.V., Alves, R.B., de Resende, M.A., Martins, C.V.B. and de Fatima, A. (2011) Schiff bases: A short review of their antimicrobial activities. Journal of Advanced Research, 2, 1-8.

5.      V.I., Prisakar, V.I., Tsapkov, S.A., Buracheeva, M.S. Byrke, and A.P. Gulya, (2005) Synthesis and antimicrobial activity of coordination compounds of copper with substituted salicylaldehyde thiosemicarbazones. Pharmaceutical Chemistry Journal, 39, 313-315.

6.      P., Przybylski, A., Huczynski, K., Pyta, B. Brzezinski, and F. Bartl, (2009) Biological properties of Schiff bases and azo derivatives of phenol. Current Organic Chemistry, 13, 124-148.

7.      J.M. Andrews, (2001) Determination of minimun inhibittory concentrations. Journal of Antimicrobial Chemotherapy, 48, 5-16.

8.      H.K. Abdullah, (2011) FT-IR and UV/Vis spectroscopic study of some Schiff bases derived from aminobenzoic acid and bromobenzaldehyde. Journal of Chemistry, 2, 1-5.

9.      H.N. Aliyu and I. Ado, (2009) Spectroscopic and potentiometric investigations of copper (II) complexes with Schiff base derived from 2-aminobenzoic acid and Salicylaldehyde. Bioscience Research Communications, 21, 215-220.

10.   J.T., Bennett, C.S., Joshua, J.D., Stephen, M.V., Christopher, D. Andreas, and A.W. Stephen, (2007) Synthesis, characterization and reactivity of Pd (II) Salicylaldimine complexes derived from aminophenols. Canadian Journal of Chemistry, 85, 392-399.

11.   N. J. P. Subhashini1, T. T.1 and Shivaraj; (Synthesis characterization and anti-bacterial activity of novel chalcone derivatives of indole); Der Pharma Chemica, 2015, 7, (3), 38-45

12.   D. N. Tai, N. D. Thanh, P.D. Nam and H. T. Duc; (1H and 13C-NMR spectra of some azomethanes of 5-amino-2-phenylindole series); Journal of Chemistry, 2007, 45 (5), 642 – 647.

13.   B. Ahmeda and T. A. Al-Howiriny; (Two New Hydroxy Chalcone Derivatives from Thymus cilicicus); Z. Naturforsch; 2007, 62b, 121 – 124.

14.   S. Molchanov and A. Gryff-Keller; (Solvation of Amides in DMSO and CDCl3: An Attempt at Quantitative DFT-Based Interpretation of 1H and 13C NMR Chemical Shifts); J. Phys. Chem. A, 2017, 121, 50, 9645-9653.

15.   Y. M. Issa, H. B. Hassib and H. E. Abdelaal; (1H NMR, 13C NMR and mass spectral studies of some Schiff bases derived from 3-amino-1,2,4-triazole); Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy); 2009, 74, (4), 902-910.

16.   J. M. Sosa, M, Vinkovi and D. V. Topi; (NMR Spectroscopy of 2-Hydroxy-1-naphthylidene Schiff Bases with Chloro and Hydroxy Substituted Aniline Moiety); Croatica Chemica Acta; 2006, 79, (3) 489-495.

17.   Z. A Naser Al-Shamkhani and H. A. Al-Hazam, "Microwave Assisted Synthesis, Characterizations and Antibacterial Activity of Some of Thiazole Derivatives", Res. J. of Pharm., Bio., and Chem., Sci., 2015, 6, 719.

18.   Z. A Naser Al-Shamkhani and H. A. Al-Hazam, "Microwave Assisted Synthesis, Characterizations and Antibacterial Activity of Some of thiazole Schiff base and azetidinone Derivatives", Chem., and Material Res., 2015, 7, 32.

 

 

 

 

 

 

Received on 02.03.2019                    Modified on 24.04.2019

Accepted on 05.05.2019                   ©AJRC All right reserved