Synthetic Approach for Novel Fluorine Substituted α-Aminophosphonic Acids Containing 1 , 2 , 4-Triazin-5-One Moiety as Antioxidant Agents

Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin5-one (6a-f) have been obtained from fluoroacylation of 6-(2ʹ-amino-5ʹ-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (1) followed by ammonilysis to give the corresponding 3-amino-derivative 3. Condensation of compound 3 with nitro/halogenated aromatic aldehydes yielded the Schiff bases 4. The simple addition of diethyl phosphonate to compound 4 produced the α-amino phosphonates 5. Acidic hydrolysis of compound 5 produced the fluorine substituted α-amino acids derivatives 6. Structures of the new compounds have been established with the help of elemental analysis and spectral measurements. Also, the products evaluated as antioxidants, where the fluorinated α-amino phosphonic acids 6 are more active than the other synthesized systems.


Chemistry
The phosphorylation of amino-organic heterocyclic systems often improves their biological activity because of the P-O bond stores energy for metabolic processes [1].Also, the chemistry of N-phosphoryl heterocyclic indicates that these compounds form dimensional polymeric chain via intermolecular [2].Moreover, the reactivity of the dipolar ion structures of the tautomeric form of α-amino phosphonates is due to the higher electron-withdrawing properties of two phenoxy and P=O groups.Thus, the α-amino-phosphonate group has a high degree of stability against any reagent attack [3].To deduce the aims of this work, 6-(2ʹ-Amino-5ʹ-nitrophenyl)-3-thioxo-1,2,4-triazin-5(2H,4H)-one (1) as a starting material obtained from reflux of 5-nitroisatin with thiosemicarbazide in aq.NaOH (Scheme 1).

Result and Discussion
The former structures of novel fluorinated α-amino phosphonic acids have been deduced from correct their elemental analysis and spectral measurements.IR spectra of both the compounds 1-6 recorded the absorption bands ῡ at 1530, 1350 cm −1 for asymmetric and symmetric NO 2 groups, 3200 -3100 and 1660 cm −1   for NH and C=O of 1,2,4-triazine, also ῡ at 1630 cm −1 attribute to CONH group and 1250 cm −1 of C-F functional groups.IR of compound 3 showed ῡ at 3300 and 1610 cm −1 stretching and bending of NH 2 group, which lacks in all the compounds 4-6.Also, the presence of ῡ at 1600 -1580 cm −1 for the exocyclic International Journal of Organic Chemistry α-amino phosphonic radicals (Figure 2 & Figure 3).
The higher stability of their base peak may be due to the tautomeric forms present and the free delocalization from HN to P=O centers (Figure 4).

The Antioxidant Evaluation
From the results obtained (Table 1) we can conclude that: Presence of CF 3 and NO 2 of 6-aryl-1,2,4-triazinone and α-amino phosphonate bearing 3-substituted amino-1,2,4-triazinones deployed a good to perfect scavenging activities.The ordering activity is 6f > 6e > 6d > 6b > 6a > 6c, which mainly attribute to the presence of C-halogen and C-NO 2 of aryl-amino derivatives.The activity of α-amino phosphonic acids 6 is higher than the activity of α-amino phosphonates 5. Also, high activity of 6f comparing with the other systems is may be due to a rich of fluorine atoms bonded to a 1,2,4-triazinone moiety, and the phosphonate groups are the potent antioxidant agent.

1, 1 -
Diphenyl-2-picrylhydrazyl (DPPH) use to produce and reduce the odd electron stable-free radical which showed a strong UV-absorption maximum at λ = 517 nm.The new systems obtained dissolved in DMSO/EtOH at 150 & 300 μmol•L −1 added to DPPH at 100 μmol•L −1 .The tube kept at room temperature for 20 minutes and the absorption measured at λ 517 nm.The difference between the test and the control taken as the percent scavenging of the DPPH radical by use the formula: % inhibition = ( ) 100 AB AA AB − ×
groups bonded to 1,2,4-triazinone bearing α-amino phosphonic acids enhance the antioxidant activities, which may use the feature of medicinal treatments.