Synthesis and Characterization of some new Schiff base Compounds derived from 4-Amino benzoic acid and study their Biological activity
Mahdi F. Radi1, Suhair S. Husain2, Abrar Natek Mohammed Zaki3, Ala`a A. Sultan4, Wejdan Mahmmod Hamed1, Wessal M. Khamis1
1Chemistry Department, College of Science , Al-Mustansiryah University, Iraq.
2Materials Research and Development Department, Ministry of Science and Technology, Baghdad, Iraq
3Industrial Research Directorate, Ministry of Science and Technology, Baghdad, Iraq
4Chemistry Department, College of Science, Diala University, Iraq.
*Corresponding Author E-mail: wessalmetaab@uomustansiriyah.edu.iq
ABSTRACT:
The present research includes the preparation of four new derivative which perfect the preparation reaction (4-amino benzoic acid)with aldehyde and ketone (aliphatic, aromatic) (acetaldehyde, benzaldehyde, acetone and benzoyl acetone) this compound are diagnosed by using some spectroscopy method (H1NMR), (I.R), (U.V), (C.H.N) and studies the physical properties (color, melting point). Finally study biological activity with bacteria (positive, negative) grams.
KEYWORDS: 4-amino benzoic acid, Acetaldehyde, Benzaldehyde, Acetone, Benzoyl acetone.
INTRODUCTION:
4-5dichloro-2-{(2Z)-2-(3-chlorobenzylidenhydrznyl)}methyl-N-phenylaniline
2-{2-hydroxybenzylidene}aminophenol
4-{1,3-benzothiazol-2-ylamino}phenol
A different types of Schiff base set in composition of Tonic drugs like the compound 2-{5-methyl-2-[iE-prop-1en1-yl]phenyl} ethanamine, which was prepared by condensation by aromatic amine and aliphatic amine (primary) with a equivalent mole ratio and presence of absolute methanol5,6, by condensation of acetophenone with 3-phenyl-2-hydrazine-1,8naphlidne) as well as by reaction of one kind of ketones with the compound 3-hydrozion-1,2,4-triazon7 which was prepared from the reaction of amino acid with aldehydes and aliphatic or aromatic ketones8,9 with derivative of p-hydroxy benzaldehyde. The reaction was achieved according of Neocliphile addition out of the hydrazide group which has pair electron on nitrogen atom and this pair hit carbon atom of carbonyl group for aldehyde compound to configure Schiff base as stable compound10.
MATERIALS AND METHODS:
1. Melting point (SMPS) Bybibbysterilin (Ltd) Ston, Staffardshinet (Made in U.K).
2. Infrared Spectrophotometer ABB. Spectrolabhorizon MBTM (Made in U.K).
3. UV-1650PSUV-Visible-spectrophotometer (Shimadzu).
4. CHNS/O Perkin Elmar 2400 (Made in U.S.A).
5. Autoclave for sterilize tools and media
6. Incubator for samples incubation.
METHODS:
For dissolving of (0.03mole) (0.411gm) from (amino benzoic acid) in 20ml of absolute ethanol which is added to (0,03mole) from Ketones or aldehydes (Benzoyl acetone, Acetone, Benzaldehyde and Acetaldehydes)11,12.
Then the mixture was refluxed for 4-5hrs), after refluxed the reactants were left to cool, filtered the formed precipitate and recrystallized by using distillate water. The reactions were achieved according the bellow equations:
Equations of preparation the derivatives
RESULTS AND DISCUSSION:
Preparation and characterization of Schiff bases:
Four new Schiff bases compounds were prepared through reacted of compound (4-amino benzoic acid) with Ketones and aldehyde (Aromatic and Aliphatic) like (Benzoyl acetone, acetone, Benzaldehyde, acetaldehyde) to form stable isomethine compounds as to the reaction mechanism and table (1) was clarified the four prepared compounds and it`s names when the table (2) referred to the physical properties of the four prepared compounds:
Mechanism of derivatives preparation for four derivatives
Table 1: The structure and names of prepared compounds:
Compound Symbols |
Compound Structure |
Compounds name according to Chem. Office |
S1 |
4-{[(1Z)-2-oxo-1-phenylpropyliden]amino} benzoic acid |
|
S2 |
4-(propan-2-ylideneamino)benzoicacid |
|
S3 |
4-{[(E)-phenylmethylidene]amino}benzoicacid |
|
S4 |
4-[(1Z)-ethylideneamino]benzoicacid |
|
Table2: Physical Properties of prepared compounds:
Colour |
Yield % |
M.P. OC |
Formal Formula |
Recrystization |
Comp |
Yellow |
85 |
198-200 |
C17H15NO3 |
Distilled water |
S1 |
White |
80 |
190-192 |
C10H11NO2 |
Distilled water |
S2 |
Orange |
80 |
179-181 |
C14H11NO2 |
Distilled water |
S3 |
red |
78 |
150-152 |
C9H9NO2 |
Distilled water
|
S4 |
Prepared compounds were characterized by using the following spectrophotometry measurements:
IR AND UV-VISIBLESPECTROPHOTOMETERS:
At First, compound (S1) [4-{[(1Z)-2-oxo-1-phenylpropyliden] amino} benzoic acid was characterized by using FTIR. IR spectra showed display of amine group for substrate 4-amino benzoic acid which should be appeared at (3460cm-1) ,as clarified at Fig.(1) which referred to 4-amino benzoic acid IR spectrum, at the same time a new band appeared at the region (1604cm-1) return to (C=N) band as showed at fig.(2)as well as appearing of a new band at (1676cm-1) referred to carbonyl group13.
Uv-visible spectra showed red-shifted to higher wave number for the transition band (290nm) and 344nm which referred to (n→π*) and (π→π*) sequentially as at fig.3. This shifted happened because of the addition new aromatic ring which was at benzoyl acetone14.
Fig.1: Showed IR spectrum of 4-aminobenzoic acid
Fig.2: Showed IR spectrum of 4-{[(1Z)-2-oxo-1-phenylpropyliden] amin} benzoic acid
Fig.3: UV-visible spectra of 4-{[(1Z)-2-oxo-1-phenylpropyliden] amin} benzoic acid
IR characterization of the second compound (S2) [4) propan-2-ylideneamino) benzoic acid showed absorption band at (1600cm-1) which return to (C=N) bond as clarified at fig.4 and briefed absence of amine group of the substrate fig. (1). Fig.4 showed appearance of carbonyl group at the region (1665cm-1) of compound (S2)15.
UV-visible spectra of the compound (S2) which showed transition band of value (λmax=349nm), (λmax=284nm) which represented the transition (n→π*) and (π→π*) respectively16.
Fig. 4: Showed IR spectrum of 4 (propan-2-ylideneamino) benzoic acid
About the compound (S3), [4-{[(E)-phenyldimethyldene] amino}benzoic acid, IR spectra showed disappearance of the band (3460cm-1), which was observed at fig. 1, that deal with amine group (-NH2) of substrate 4-amino benzoic acid with appearance of new band deals with (C=N) group at the region of (1600cm-1)12 as well as the band at the region of (1731cm-1) deals with the carbonyl group. All these transition bands was clarified at the Fig. (5). Uv-visible spectra observed transition value at the region of (256nm),(340nm) deal with the electronic transitions (n→π*),(π→π*) respectively as them clarified at fig(6)17.
Fig. 5: Showed IR spectrum of 4-{[(E)-phenylmethylidene] amino} benzoic acid
Fig. (6): UV-visible spectrum of 4-{[(E-phenylemethylidene] amino} benzoic acid
Finally, Compound (S4) was characterized by using IR spectra. IRspectra showed 4-[(1Z)-ethylideneamino] benzoic acid showed absorption band return to (C=N) group at the region (1615cm-1) beside of absence of band (3460cm-1) which deal with (-NH2) group and appearance of carbonyl group band at the region (1715cm-1) as briefed at fig.(7)18.
About the electronic spectra of compound (S4), it`s clarified that uv-visible spectra showed two bands at electronic bands at the regions (368nm,261nm) return to the electronic transition (n→π*) and (π→π*) respectively [11], as Fig. (8)19.
Fig.7: Showed IR spectrum of 4-[(1Z)-ethylideneamino] benzoic acid
Fig. 8: UV-visible spectrum of 4-[(1Z)-ethylideneamino]benzoic acid
Table 3: showed all IR and electronic spectra values for all prepared compounds.
NO. COMP |
U.V nm λmax |
Characteristic band of I.R spectra (cm-1. KBr disc) |
|||||||
(C- H)al |
(C- H)Ar |
(C=O) |
(O-H) |
(C=N) |
(C=C) |
(C-N) |
(C- H)al |
||
S1 |
344 290 |
2876 |
2964 |
1676 |
3412 |
1604 |
1516 |
1260 |
S1 |
S2 |
349 284 |
2826 |
2973 |
1665 |
3359 3420 |
1600 |
1522 |
1291 |
S2 |
S3 |
340 256 |
2853 |
2923 |
1731 |
3478 |
1600 |
1457 |
1179 |
S3 |
S4 |
368 261 |
3008 |
2980 |
1715 |
3418 |
1615 |
1364 |
1034 |
S4 |
Table 4: Showed the values of elemental analysis
Name of Compound |
Workable |
Theoretical |
Formula |
Sym |
||||
N% |
H% |
C% |
N% |
H% |
C% |
|||
4-{[(1Z)-2-oxo-1-phenylpropyliden] amino} benzoic acid |
5.26 |
4.94 |
72.5 |
4.98 |
5.32 |
72.59 |
C17H15NO3 |
S1 |
4-(propan-2-ylideneamino) benzoic acid |
8.2 |
5.8 |
66.9 |
7.82 |
7.26 |
67.03 |
C10H13NO2 |
S2 |
4-{[(E)-phenylmethylidene]amino}benzoic acid |
9.10 |
6.10 |
67.0 |
8.41 |
4.93 |
66.66 |
C9H8NO2 |
S3 |
4-[ (1Z)-ethylideneamino} benzoic acid |
5.70 |
4.64 |
73.9 |
6.16 |
5.72 |
74.00 |
C14H13NO2 |
S4 |
Values of elements analysis (C.H.N) for prepared compounds were calculated and the practical, theoretical as shown at the table (4) that briefed the practical and theoretical values for Carbon, Hydrogen and Nitrogen. The practical values was obtained by using (CHNS/O PERKIN Elmar 2400) apparatus which showed agreement between the practical and theoretical values20.
BIOLOGICAL ACTIVITY STUDY:
Different researches and papers proved that Schiff bases compounds have biological effect against different kinds of Positive and negative bacteria to the gram pigment21 where the adopted method was the spread method by agar. Where was used the drilling. At the same time, this method is called (Kerby-Bauer) too22.
At biological activity Schiff base derivatives testing, First kind of test was negative bacteria to gram pigment (Pseudomonas aenuginosa) and the other positive bacteria (Bacillus cereus) where the nutrient ager was prepared to activate the bacteria for 24hrs. The same medium was used to make the activity test of Schiff bases compounds which made for the four prepared compounds as listed below:
4-{[(1Z)-2-0x0-1-phenylpropyliden] amino}, 4-(propan-2-ylidenamino) benzoic acid, 4-{[(E)–phenylmethylidene] amino} benzoic, 4-[(1Z)-ethylideneamino] benzoic acid. This test was achieved by take amount of growing bacteria in solid medium for 24hrs and diluted with distillated water which equalized (1.5×108). These sample where putted orthogonal planning on nutrition medium and solid with the using of corkscrew to make holes with a diameter of 7mm. These holes fulfilled with pervious prepared concentration. After this, bunch of dishes airily at 37̊C for 24hrs. It was observed after bunched the dishes inhibition region around of the holes as shown at fig.(9) and fig.(10) , Table (5) clarified the effect of compounds of used bacteria kinds. From Table (5) , it`s clarified that compound 4-(propan-2-ylideamino)benzoic acid which was contributed with two concentration (0.14mg/ml) and (0.16mg/ml). The concertation (0.16mg/ml) that was the more activity against studied bacteria because it was effected against negative of gram pigment (Pseudomonas aeruginosa) and positive (Bacillus cereus)23,24.
Table 5: Showed the effect of prepared compounds on used bacteria
S2 0.16mg/ml |
S3 0.1mg/ml |
0.14mg/ml |
S4 0.1mg/ml |
S1 0.08mg/ml |
Bacteria type |
22 |
---- |
20 |
15 |
9 |
Pseudomonas aenuginosa |
30 |
10 |
17 |
12 |
10 |
Bacillus cereus |
Fig. 9: Showed the inhibition region of prepared compound (Pseudomonas aeruginosa)
Fig. 10: Showed the inhibition region of prepared compound (Bacillus cereus)
ACKNOWLEDGEMENT:
Thanks should be submitted to my university (Mustansiriyah University) for all helps submitted to achieve this research. Thanks gave for Head of Chemistry Department and Dean of Science College. Also authors thankful for chemistry laboratories memberships for all helps they gave it to complete this work.
CONFLICT OF INTEREST:
All authors declare that there is no conflict of interest regarding the publication of this paper.
REFERENCES:
1. Duport C., Zigha A., Rosenfeld E. and Schmitt P. Control of enterotoxin Gene Expression in Bacillus cereus F4430|73 Involves the Signal Transduction System. J Bacteriol. 2006;188: 6640-6651.
2. B. Sun J., Chen J., Lix. Y.Hu, J.Chin.Chem.Soc,2001;12,1043.
3. Tidwell T. T. Hugo (ugo).Schiff bases and a century of b-lactam Synthesis .Angew. Chem .Int.Ed.,2008;47:1016-1020.
4. Boghae lD. M. and Mohebi S. Tetrahederon ,2002;58:5357.
5. Ashraf Muhammad Aqeel, Mahmood Karamat and Wajid Abdul. Synthesis, Characterization and Biological Activity of Schiff Bases. IPCBEE ,2011;10.
6. Liu S.Y., and Nocera D.G. Tetrahedron let.,2006;47:1923.
7. Lafta J. Suad. Synthesis of New Derivative For 5-trizolo-[3,4-b] Thiazolidine-4-one. Al-Mustansiriyah Journal Sci. Baghdad Iraq,2007;18:32-37.
8. BudakotiA., Abid M. and AzamA.Eur.J.Med.Chem.2006;41:63.
9. Naeimi H., Sharghi H., Salami F. and Rabiel Kh. Hetero at.Chem.2008;19:43-47.
10. Axel G Griesbeck, Marco Franke, JörgNeudörfl, and Hidehiro Kotaka. Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies. Beilstein J Org Chem.2011; 7: 127–134.
11. Wessal M Khamis, Bayader F Abbas, Shayamaa H Abd-Al-Sada, Mustafa Taha Mohammed, Alaa A Sultan, Nedhal M Khamim. Preparation, Investigation and Enzymatic Activity of Mixed Iigand Complexes of Mefenamic Acid and Phenyl Alanine with some Transition Metal. Journal of Engineering and Applied Sciences.2019;14(3): 734-743
12. Al-Zaidi Basim H., Ismail Ahmed H., Naseaf Ali N. and Khamis Wessal. Preparation, Characterization and Biological Activity of New Tridentate Imine-Oxime Ligand (H2L) and Its Metal Complexes`` Asian J. Chem.,2018, 30(5):1157-1164.
13. M. Issa Raafat , M. Khedr Abdalla, Rizk , Helen F. UV–vis, IR and 1H NMR spectroscopic studies of some Schiff bases derivatives of 4-aminoantipyrine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy.2005;62(1-3): 621-629
14. Cinarli Adem, Gürbüz Demet, Tavman Aydin and Birteksöz A. Seher. Synthesis, Spectral Characterizations And Antimicrobial Activity Of Some Schiff Bases Of 4-Chloro-2-Aminophenol. Bull. Chem. Soc. Ethiop. 2011; 25(3):407-417
15. Khalil Mostafa M. H., Ismail Eman H., Mohamed Gehad G., Zayed M. and Badr Ahmed. Synthesis and characterization of a novel schiff base metal complexes and their application in determination of iron in different types of natural water. Open Journal of Inorganic Chemistry, 2012; 2: 13-21
16. Issa Raafat M., Khedr Abdalla M. and Rizk Helen. 1 H NMR, IR and UV/VIS Spectroscopic Studies of Some Schiff Bases Derived From 2-Aminobenzothiazole and 2-Amino-3-hydroxypyridine. Journal of the Chinese Chemical Society.2008;55:875-884
17. M. J Jisha and Sobana Raj C. Isac .Synthesis and characterization of Schiff base complexes of Cu(II), Ni(II), Co(II) complexes of Schiff base derived from furan 3- carboxaldehyde and 3- amino pyridine. International Journal of Scientific and Research Publications.2017;7(10):10-19.
18. Theodore Jenisha S. and David J P. Schiff Base Ligand Its Complexes And Their FT-IR Spectroscopy Studies. International Journal on Applied Bioengineering. 2015;9(1).
19. Sharma Anita and Shah Manish. Synthesis and Characterization of some Transition metal complexes derived from Bidentate Schiff Base Ligand. Journal of Applied Chemistry 2013;3(5):62-66
20. Majeed Nesreen N., Al-Fregi Adil and Abbas Fahim. Synthesis and Characterization of Some New Schiff bases Derived from ferrocene compounds. Journal of Kerbala University .2012;10 (3):328-338.
21. Jeroen J. Baert, Jessika De Clippeleer, Paul S. Hughes, Luc De Cooman, and Guido Aerts.On the Origin of Free and Bound Staling Aldehydes in Beer. J. Agric. Food Chem., 2012; 60 (46):11449–11472.
22. Joshi. H., Kamounah F.S and Gooijer C., Van derzwan G and AntonovL., J. of photochemistry and photobiology. A. chemistry,2002;152:183-191.
23. Allcock S. , Young E. H. , Holmes M. , Gurdasani D. , Dougan G., Sandhu M. S. , Solomon L. and Török M. E. .Populations: challenges and opportunities. Glob Health Epidemiol Genom. 2017; 2, e4.
24. Duport C., Zigha A., Rosenfeld E. and Schmitt P. Control of enterotoxin Gene Expression in Bacillus cereus F4430|73 Involves the Signal Transduction System.J.Bacteriol.2006;188: 6640-6651.
Received on 23.08.2018 Modified on 14.01.2019
Accepted on 04.03.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(5):2207-2212.
DOI: 10.5958/0974-360X.2019.00368.8