Synthesis ,Characterization and Antioxidant Activity of Schiff base derivatives from [6,6'-(1,4-phenylene)bis(4-(4-aminophenyl) pyrimidin)]

Two Hetreterocyclic compounds prepared from condensation reaction of Bis chalcone([3,3(1,4-phenylene)bis(1(4-aminophenyl)prop-2-en-1-one]with thiourea and urea By condensing a novel six-member heterocyclic (pyrimidene ring) with the suitable aromatic, new substituted azomethines of ( o, m, and p ) hydroxy benzaldehyde with heterocyclic substituents were created. By using NMR and FTIR spectroscopy, the novel heterocyclic compounds and these derivatives of schiff bases were identified. A DPPH free radical scavenging assay was performed on the synthesized compounds, and the heterocyclic substituted thiol group and its Schiff base derivative demonstrated remarkable antioxidant activity.


Introduction
German scientist Hugo Schiff (1864-1915) is mentioned.He found some bases and gave them the name Schiff bases (1) .Under particular circumstances, a primary amine reacts with carbonyl (aldehydes or ketones) to produce schiff bases.The major function is imine or azomethine (-C=N-) group because the general structure is R 1 R 2 C=NR (R= H). ( 2)

Scheme 1: General formation of Schiff bases
A variety of pharmacological and biological actions, including antibacterial, cytotoxic, antifungal, antimalarial, anticonvulsant, antioxidant, and antiinflammatory properties, were demonstrated by Schiff bases, particularly those associated with heterocyclic moiety (3,4).
Heterocyclic compound is the class of cyclic organic compounds those having at least one heteroatom (i.e.atom other than carbon) in the cyclic ring system.The most common heteroatoms are nitrogen (N), oxygen (O) and sulphur (S).Chalcones are thought to be one of the most beneficial sources of heterocyclic compounds.Due to their extensive biological activity, these compounds and their derivatives are regarded as some of the top medicinal chemistry molecules (5).
Chalcone undergoes a cyclization reaction under specific conditions to produce these heterocyclic rings with five, six, and seven members pyrimidine ring example for Six membered unsaturated aromatic heterocyclic conmpound, scheme (2) (2) It was once believed that pyrimidines (also known as "m-diazine") were the byproducts of nitric acid's oxidation of uric acid.Pyrimidin ring containing two nitrogen atoms at positions 1 and 3 of the six-membered rings.(6)
Bis-Chalcone (0.004 mol) was refluxed with Thiourea (0.009 mol) in toluene solvent (20 ml) and a catalytic a small amount of glacial acetic acid at 80 O C for 24h.The reaction was monitored by TLC using (Chloroform : Methanol) (9.5 ml + 0.5ml).
After the reaction was finished, the precipitate was filtered, dried, and recrystallized with toluene to produce the desired product, which had a melting point of 150-152 o C and a yield of 60%, dark brown powder.
Bis-Chalcone (0.004 mol) and urea (0.0010 mol) were refluxed in toluene (20 ml) for 24 hours at 80 o C with catalytic addition of a little amount of glacial acetic acid after 15 minutes.TLC and (Chloroform: Methanol) (9.5 ml + 0.5 ml) were employed to monitor the reaction.
After the reaction is finished, In order to produce the desired product with the specified melting point (260 o C decomposition) and yield (64%) was produced, an oily substance was generated, which was removed from the solvent and washed with ethanol.Crystals were then formed, which were separated, dried, and cleaned by ethanol.

Synthesis Schiff bases derivative from heterocyclic compounds and (o,m and p) hydroxy benzaldehydes
Schiff base was prepared as mentioned in the literature (10) .In our research Schiff base compounds were synthesized by the reflux condensation reaction of (o,p,m)-hydroxybenzaldehyde compounds (0.003mole) along with (0.001mole) diamine heterocyclic compounds(Scheme 3) using 15ml absolute ethanol as solvent in addition of a small amount of p-toluene sulphonic acid as catalyst.The oily or powder were obtained after (48) hours dried at room temperature.Diethylether was used for washing and product was recrystallized with ethanol and dried at room temperature.

Results and discussion
The synthesis heterocyclic derivative from Bis-chalcones and their was carried out in accordance with Scheme (3), and Table (1)contains physical information on these compounds.The initial chalcone, [3,3(1,4-phenylene) bis(1(4aminophenyl)prop-2-en-1-one], was created using the Claisen-Schmidt reaction of 4-aminoacetophenone with Terphthaldehyde in ethanol in the presence of aqueous sodium hydroxide at room temperature.In acid medium at 80 O C, the Bis-chalcone and Thiourea (or urea) were allowed to react for 24 hours to obtain pyrimidine rings, these compounds are shown in scheme ( 3)
Schiff base compounds were synthesized by condensation reaction of hydroxyl benzaldehyde drevitives (0.001mole) along with (0.003mole) diamine heterocyclic compounds at 70-80 o C temperature in acid medium.The physical properties of these compounds in the table (4) and the synthetic route to the compounds is outlined in Scheme (4).Figures (3) to (8), revealed the elimination of the amine band for heterocyclic compounds in the range of (3100-3300) cm -1 and the carbonyl band for aldehyde compounds in the region of (1700-1770 ) cm -1 .The stretching frequency of the azomethine group in the range (1600 -1690) cm -1 caused a new unique medium to strong intensity band to form in the spectrums.
The FTIR spectra of all the prepared compounds showed a wide and distinct band in the region (3000-3500) cm -1 due to the hydroxide groups.Table (5) displays the results for these chemicals' absorption bands The singlet signal at position (6.07ppm), which is a member of the amine group of heterocycles, vanished from the 1H NMR spectra of Schiff bases generated in Figures (11)(12)(13)(14)(15)(16).This shows how aldehyde compounds' amine group and carbonyl group interact.
It was also found the emergence of a new signal belonging to the azomethine group within the range δ ( 9.67-8.17)ppm.The spectra also showed a singlet signal due to the hydroxyl groups within the range δ (10.26-8.76)ppm.As well as found multiplet signal to aromatic rings located between δ (7 -8.5) as shown in the table below(6) It was also found that all derivatives gave a doublet signal within the range δ (5-8) ppm due to the proton of the heterocyclic ring.

Antioxidant activity
The DPPH assay is carried out under the assumption that an antioxidant reduces (decolorizes) DPPH free radicals by acting as a hydrogen donor.Scheme (One technique to gauge a substance's antioxidant strength is to assess its ability to scavenge DPPH, which can be done by observing a decrease in the maximum DPPH absorption at 570 nm (14).The compound (2) and Schiff bases derivative it's appeared antioxidant activity compare with the compound (3) and its derivative.The antioxidant activity of the created heterocyclic compounds was shown in table (7)

Scheme (5) principal of the antioxidant DPPH assay
The table (8)(9)(10)(11) displayed the %RSA and IC50 for compounds that were antioxidant actives, with the IC50 values calculated from formulae on charts of the curves in the figures (17-20)

of Kufa for Chemical Sciences Vol. ( 321Table ( 1
) Physical properties o f synthesized compounds (in scheme 3)

Table ( 2
): The FT-IR data of the synthesized heterocyclic compounds

of Kufa for Chemical Sciences Vol. ( 324Table ( 5
): The FT-IR data of the synthesized Schiff Bases compounds