Research Journal of Chemical Sciences ______________________________________________ ISSN 2231-606X Vol. 5(4), 53-56, April (2015) Res. J. Chem. Sci. International Science Congress Association 53 Synthesis of New Sulfa-Nitrone Compounds Abood Huda S., Majeed Nisreen N. and Al-najarAnis A.2 Department of Pharmaceutical chemistry, College of Pharmacy, University of Basrah, Basrah, IRAQ Department of Chemistry, College of Science, University of Basrah, Basrah, IRAQAvailable online at: www.isca.in, www.isca.me Received 8th April 2015, revised 14th April 2015, accepted 17th April 2015 AbstractThe Schiff bases were synthesized from sulfa drugs with some aldehyde and then converted to nitronesby oxidation of Schiff bases with peracetic acid which synthesized by using of hydrogen peroxide with acetic acid.The resulting products were identified by physical properties like melting point (m.p.), retardation factor (R) and color. Also compounds showed the expected data in identification techniques like FTIR, HNMR, mass spectroscopy and Elemental analysis (CHN). The results verified the chemical structures of synthesized compounds. Keywords: Nitrone, sulfa drugs, Schiff base, sulfa-nitrone. Introduction Nitrones have taken special interests due to their successful applications as building blocks in the synthesis of various natural and biologically active compounds. They are commonly used precursors2 in the synthesis of a variety of heterocycles, as spin trapping reagents, in the identification of transient radicals3,4 and as therapeutic agents. Oxidation of imines by peroxide acids gives a mixture of nitrone and oxaziridine, as shown in scheme-1. Scheme-1 There is a competition between the formation of nitrone and oxaziridine compounds. Many factors affect the formation of the product ratio, such as less bulky substituents on the imino-N-atom and non hydroxylic solvents. Spontaneous rearrangement of oxaziridines into nitrones is observed, either upon heating or treatment with acids. The reaction between imines and hyrdoperoxides was also employed to the synthesis of a variety of 3-aryloxaziridine derivatives, which were rearranged by heating to corresponding nitrones, as shown in scheme-2. Scheme-2 R, R1=Alkyl or aryl group. Material and Methods A series of Schiff bases were synthesized in order to study them and to synthesize the nitrone compounds. The general structures of Schiff bases and nitronesare illustrated below in figure-1. N H R1 S R2 O O R1 = , OH , O2N H3C R2 = NH NH and N H R1 S R2 O O O Schiff basenitrone S ,, NH Figure-1 The general structures of Schiff bases and nitrones Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(4), 53-56, April (2015) Res. J. Chem. Sci. International Science Congress Association 54 General method to synthesize Schiff bases: The procedure of which is according to the following: To (0.028 mol) of sulfa drug (160 ml) of absolute ethanol was added (0.028 mol) of aldehyde were mixed in (250 ml) round bottom flask. To the reaction mixture 3 drops of glacial acetic acid were added as catalyst. The reaction mixture was refluxed for several hours according to the type of substrate as shown in Table-1 and then the mixture was cooled overnight. The precipitate was filtered and purified by recrystallization from absolute ethanol10. The different Schiff bases were prepared and studied in this research. Schiff bases were formed by the condensation reaction of some aldehydes such as benzaldehyde, salicyaldehyde, p-nitro and p-hydroxy benzaldehyde with sulfa drug such as sulfadiazine, sulfamerazine, sulfamethoxazole, sulfaguanidine, sulfisoxazole and 4,4`-diamino diphenylsulfone, in absolute ethanol with elimination of water at the end of the reaction, as shown in scheme-3. C H O X + S H2N R O O Abs. EtOH-H S N R O O C X X= H, OH, NO2 R=sulfa drug residue Scheme-3 Table-1 The symbol, time of reaction and structure of Schiff bases Symbol Time of reaction hours Structure S1 8 O H NSOO N H 2 S2 30 S3 15 O NN O H NHNH 2 S4 11 S5 12 O HSNN O H The mechanism of the reaction, as illustrated in scheme-4, included the nucleophilic attack of an amine at the carbon atom of carbonyl group. O H SO H2N C OH N+ H H SO C N OH SO C N SO H -H H -H C N SO + .. Scheme-4 The mechanism of the formation of Schiff baseSynthesis of nitrone: These compounds were prepared agreed literature11.In 50ml round bottom flask, 0.002 mole of an imine and peracetic acid prepared from mixture of 0.013 mol (1.2 ml) 36% H with (2.5 ml) from glacial acetic acid were added, during this addition, the solution was cooled to -5C. After the addition is complete, the reaction mixture was kept below 10C with continuous stirring in dark over a period of 3 hours, and then left at 0C for 24 hours. The solid was removed by filtration and washed with two portions of 5ml of acetone, ethanol, then tasted by KI-Starch paper to indicate removed any unreacted H. The precipitate nitrone was recrystallized from absolute ethanol. A series of nitrone compounds have been synthesized and studied in our research. All these compounds were synthesized by the oxidation reaction of Schiff base with peracetic acid, as shown in the mechanism below. Then the peracetic acid was added drop by drop to Schiff base that was placed in ice bath in temperature between -5 to -10 C. The oxidation was carried out due to the suggested mechanism, as shown in scheme-5. All these reactions were monitored bythin layer chromatography TLC. -------(c) Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(4), 53-56, April (2015) Res. J. Chem. Sci. International Science Congress Association 55 H3C OH O OO H H H 3 C O O O H R2 H N OOH CH N R 1 R2 OOH CH OO CH 3 H +H R 1 R2 H N R1 O Scheme-5 The suggested mechanism of nitrone formation From this mechanism we proved, with regard to the oxygen transfer to the C=N in Schiff base, that the observed lack of stereo retention in the oxidation of cis- and trans-acyclic substituted Schiff bases, which indicates a stepwise oxygen atom transfer process. However, there is insufficient evidence to fully elucidate whether oxygen transfer to the C=N Schiff base occurs via the peroxy species.The purification of nitrone compounds was tested first by thin layer chromatography TLC using different eluents. The best separation was obtained in mixture of (n-Hexane: Ethyl acetate) having a ratio (3:2), respectively as eluent. Accordingly, the compounds were purified by column chromatography using the above eluent. Results and Discussion The resulting data were obtained for the synthesised compounds from analysis data as following: (Z)-4-(4-aminophenylsulfonyl)-N-(2-hydroxybenzylidene) aniline oxide(N1) melting point (m.p.) 205-208C, yellow needles yield 83%, TLC,DCM:CHCl 2:3, retardation factor R= 0.43, FTIR /cm-1: 1616 (C=N), 1135 (N-O), 3365 (OH), 3120 (NH).HNMR(500 MHz, dimethyl sulfoxide (DMSO)); : 8.96(s, CH=NO), 7.59-8.06 (AA`BB` Harom), 6.99-7.70 (m, arom), 12.39 (s, OH). Mass (m/z): 368 [M], 185, 142, 120, 92. For C1916S (found): 62.09 % C, 4.31 % H, and 6.82 % N. (Z)-N-butylidene-4-(N-(diaminomethylene)sulfamoyl) aniline oxide (N2) m.p. 230-231C, orangneedles yield 87%, TLC, n-hexan: EtAC 3.5:1.5, R= 0.73, FTIR /cm-1: 1622 (C=N), 1180(N-O), 3220, 3344(NH).HNMR (500 MHz, DMSO); : 9.73 (s, CH=NO), 7.62-8.04 (AA`BB` Harom), 7.29 and 7.34 (t, d, Hguanidine), 2.34 (m, 2H, CH), 2.12 (q, 2H, CH) 1.24 (t, 3H, CH). Mass (m/z): 284 [M], 256, 213, 198, 185, 167, 71, 69. For C1118S (found): 45.96 % C, 5.94 % H, and 19.49 % N. (Z)-4-(N-(diaminomethylene) sulfamoyl)-N- (2-hydroxy benzylidene) aniline oxide(N3)m.p. 220-223 C, yellow-brown fine needles yield 75%, TLC, benzene: CHCl 3:7, R= 0.55, FTIR /cm-1: 1618 (C=N), 1132 (N-O),3444 (OH), 3224, 3353 (NH). HNMR (500 MHz, DMSO); : 8.98 (s, CH=NO), 7.51-7.82 (AA`BB` Harom), 6.99-7.79 (m, Harom), 6.73 (m, br, guanidine), 12.70 (s, OH). Mass (m/z): 334 [M], 318, 142, 121, 105, 94. For C1414S (found) 50.32% C, 4.18 % H, and 16.90 % N. (Z)-N-(2-hydroxybenzylidene)-4-(N-pyridin-2-ylsulfamoyl) aniline oxide (N4) m.p. 215-217C, yellow-brown fine needles yield80%, TLC, benzene: CHCl 3:7, R= 0.68 , FTIR /cm-1: 1627 (C=N), 1138 (N-O), 3128(NH). HNMR (500 MHz,  \n \n \r\n\n\n\r-7.94 (AA`BB` Harom), 6.96-7.69 (m, Harom), 6.73, 12.57 (s, OH). For C1815S (found): 58.48 % C, 4.12 % H, and 11.51 % N. (Z)-N-(2-hydroxybenzylidene)-4-(N-thiazol-5-ylsulfamoyl) aniline oxide (N5)m.p. 227-229 C, red-brown needles yield 79%, TLC, n-hexane: EtAc 3:2, R= 0.49, FTIR /cm-1: 1616 (C=N), 1182 (N-O),3498(OH), 3145(NH). HNMR (500 MHz,  \n \n \r\n\n\n\r-7.87 (AA`BB` Harom), 6.99-7.69 (m, Harom), 6.86,7.38 (d,dHthiazole), 12.60 (s, OH). Mass (m/z): 375 [M], 213, 137, 121, 83. For C1613(found) 52.06 % C, 2.95 % H, and 11.31 % N. Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(4), 53-56, April (2015) Res. J. Chem. Sci. International Science Congress Association 56 The relevant IR spectral bands that can provide from appear of band (N-O) in the range (1132-1182 cm-1)12 that verify convert of Schiff bases to nitrones. In HNMR spectra obtianed bands in the range (8.96-9.73 ppm) which belongs to nitrone groups (s, CH=NO)13. Mass spectrscopy give the molecular ion and other fragments which indicated the stracture of prepared nitrones. The elemental analysis fond resemble to theoritical values. The intermediate form throughout the reaction undergoes elimination of water to yield the appropriate Schiff base. The yield of products depends on the type of substituted groups. Therefore, the presence of electron donating groups in amine and electron withdrawing groups in an aldehyde increases the yield of products or vice-versa. As an example, the yield of S2 was 87% more than S1 75%, and also in N2 the yield was 87% while N1 the yield was 83%. Conclusion New nitrone were obtained from oxidation of Schiff bases by peracetic acid. This method was easier than other methods to produce nitrone. The Schiff bases were synthesised of some sulfa drugs with different aldehyde compounds. The chemical structures of new sulfa-nitrone compounds were characterized by identification methods. References 1. Breuer E., Aurich H.G. and Nielsen A., Nitrones, nitronates and nitroxides, chapter 3, New Jersey, John Wiley and Sons, (1989) 2. Sridharan V. , Muthusubramanian S., Sivasubramanian S. and Polborn K., Diastereoselective synthesis of 2, 3, 4, 5-tetrasubstituted isoxazolidines via 1, 3-dipolar cycloaddition, Tetrahedron, 60(40), 8881-8892 (2004) 3.Villamena F.A. and Zweier J.L., Detection of reactive oxygen and nitrogen species by EPR spin trapping, Antioxid. Redox Signal, 6(3), 619-629 (2004) 4. 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