PowerPoint Presentation

Thesis Presentation.

Supervisor. Ms. Tahira Saleem Assistant Professor Department of Chemistry The Women University Multan.

Introduction. Materials and Methods. Results and Discussion.

Introduction.

Introduction. The main focus of this thesis is “to synthesize thiosemicarbazones that are expected to have potential pharmacological activities” such as: Analgesic Antibacterial anti-HIV, etc. Generally, heterocyclic compounds have evoked interest and concern because of their fundamental role in biological activity and biological actions in nature [1]. To efficiently design and synthesize biologically active molecules and new heterocyclic compounds with potential chemotherapeutic activities are the key challenges of topical chemistry [2, 3]. The demand for new testing compounds has tremendously increased by the discovery of high-throughput screening and, therefore, MCRs (multi-component reactions) became progressively useful tools to synthesize biologically active compounds as MCRs can dramatically lessen the production of chemical waste [4]..

10-Figure2-1. Introduction. Multi-component reactions Type of reaction used to synthesize novel thiosemicarbazones is a one-pot processes where three or more compounds react to form a single product. By definition, multicomponent reactions are those reactions whereby more than two reactants combine in a sequential manner to give highly selective products that retain majority of the atoms of the starting material [5]..

The selective conversion of carbon–oxygen bonds into carbon–nitrogen bonds to form amines is one of the most important chemical transformations for the production of bulk and fine chemicals and pharma intermediates. An attractive atom-economic way of carrying out such C–N bond formations is the direct N-alkylation of simple amines with alcohols by the borrowing hydrogen strategy . To make a huge variety of thiosemicarbazones , thiosemicarbazide is usually fused with aldehydes or ketones . It may be used to make: Thienopyrimidine urea derivatives, Thiosemicarbazides and 2-amino thiadiazole, among other heterocycles and bioactive compounds..

Here is the brief introduction of the main constituents and the type of reactions used to synthesize Thiosemicarbazones . Main constitutents 5-amino-3-methylisoxazole 2-hydroxy-1,4-naphthoquinone Terephthaldehyde and Thiosemicarbazides Reactions: Multicomponent Reactions.

Document1-page0001 (1). 5-amino-3-methylisoxazole.

2-hydroxy-1,4-naphthoquinone or lawsone. 2-hydroxy-1,4-naphthoquinone (M.P. 196.95 º C ) is an important derivative of 1,4-naphthoquinone. This compound is extracted from natural sources such as henna ( Lawsonia inermis or Lawsonia alba ) [7]. Recently, it has been investigated that henna has clinical effectiveness for the treatment of moniliasis & amoebiasis and 2-hydroxy-1,4-naphthoquinone is effective for sickle cell anaemia [8,10]. However, there are some reports about the toxicity of 2-hydroxy-1,4-naphthoquinone..

abstract. Biological action of certain lawsone derivatives.

Semithiocarbazides which are convenient reactants have been widely used to synthesize heterocycles. Thiosemicarbazides are subjected to a wide range of reactions that result in the formation of novel chemical species. The widespread application of C-N and C=N bonds ( as opposed to N-N bonds formation ) for the construction of the heterocycles in good yields reflects their utility at large scale [11]..

Aim of Project.

A variety of novel heterocyclic derivatives due to their importance in medical field are synthesized by using 5-amino-3-methylisoxazole , terephthalaldehyde and 2-hydroxy-1,4-naphthoquinone in one-pot reaction. The Aims of My Project are: Synthesis of 4-(3-methyl-5,10-dioxo-4,5,10,11-tetrahydrobenzo[g] isoxazolo [5,4-b]quinolin-4-yl)benzaldehyde by reacting 5-amino-3-methylisoxazole , terephthalaldehyde and 2-hydroxy-1,4-naphthoquinone . Synthesis of Semithiocarbazones by reacting 4-(3-methyl-5,10-dioxo-4,5,10,11-tetrahydrobenzo[g] isoxazolo [5,4-b]quinolin-4-yl)benzaldehyde with several semithiocarbazides , such as: i. Benzyl thiosemicarbazide ii. Cyclohexyl thiosemicarbazide iii. 4-fluoro phenylthiosemicarbazide iv. 4-tolyl thiosemicarbazide v. Methyl thiosemicarbazide vi. 3-nitrophenyl thiosemicarbazide vii. 2,4-dimethylphenyl thiosemicarbazide viii. 3-methoxyphenyl thiosemicarbazide ix. 4-nitrophenyl thiosemicarbazide.

abstract. abstract. abstract. . . Thiosemicarbazides.

. . . abstract. Thiosemicarbazides.

Materials and Methods.

Instrumentation The reaction was performing by ultrasonic and its model is Elmasonic E 60 H, and ceramic hot plate stirrer was used with model MGST1-V2 of Eisco scientific USA. The pipetman of France and eppendorf was also used in this reaction. Reagents and Solvents: All reagents an solvents were used as obtained from suppliers, recrystallized or re-distilled as necessary. Melting Points: Melting point was taken on GallenKemp melting point apparatus which are uncorrected of the synthesized compounds. Thin Layer Chromatography (TLC): TLC was performed by using aluminium sheets (Merck) coated with silica gel 60 F 254 . Infra-Red Spectra: FTIR spectra were recorded in the spectral range by using standard methods on Bruker Tensor 27 with model ALPHA-E..

Reactions.

An equi-molar mixture of 2-Hydroxy-1,4-naphthoquinone, terephthaldehyde and 5-Amino-3-methylisoxazole was dissolved in 7 ml ethanol and refluxed for 6 hours. Then, the reaction mixture is allowed to stand upto 24 hours. After completion of the reaction, centrifuged and washed with ethanol in order to remove impurities and then air dried. On a silica gel, the residue was chromatographed, eluting choloform: methanol (CH 3 OH) in ratio of 9:1, respectively, to get pure product..

abstract. Mechanism of Reaction.

abstract. General Procedure for Thiosemicarbazones Derivatives: Thiosemicarbazones was prepared by reacting 4-(3-methyl-5,10-dioxo-4,5,10,11-etrahydrobenzo[g] isoxazolo[5,4-b]quinolin-4-yl)benzaldehyde with several semi thiocarbazides by using p- TsOH (10%) as a catalyst and the reaction mixture was refluxed for 6-8 hours. After completion of the reaction, centrifuged and washed with ethanol in order to remove impurities and then air dried. The residue was chromatographed on silica gel eluting chloroform: methanol (9:1) to get pure product..

abstract. Mechanism of Reaction.

. Mechanism of Reaction.

Results and Discussion.

Results and Discussion. Comp no. Structure Yield Melting point º C Color R f value 82 78% 643.65 º C Blood red 0.87 83 78% 645.02 º C orange 0.67.

Comp no. Structure Yield Melting point º C Color R f value 84 72% 643.65 º C brick red 0.90 85 64 % 646.65 º C brick red 0.77.

Comp no. Structure Yield Melting point º C Color R f value 86 79 % 647.21 º C red 0.79 87 82% 644.31 º C red 0.58.

Comp no. Structure Yield Melting point º C Color R f value 88 69% 644.56 º C red 0.68 89 72% 643.98 º C orange red 0.86.

Comp no. Structure Yield Melting point º C Color R f value 90 67% 644.67 º C orange 0.71 91 73 % 644.87 º C orange 0.80.

Solubility of Thiosemicarbazones (82-91). Compound no. Ethyl acetate Ethanol Chloroform n-hexane Methanol DMSO (82) S S S IS S S (83) S PS S IS S S (84) S IS S IS S S (85) S IS S IS S S (86) S IS S IS S S (87) S PS S IS S S (88) S IS S IS S S (89) S IS S IS S S (90) S IS S IS S S (91) S IS S IS S S.

Major IR Bands of compound (82). Compound no. 3500-3000 cm -3 3000-2600 cm -3 2500-1500 cm -3 1500-1000 cm -3 1000-500 cm -3 (82) 3291 2030.43 1653.44 1508.20 1457.35 1338.56 720.86 Band assignment -NH Stretching -CH (Alkyl) stretching Aromatic -C=N- Stretching -C-N- Stretching Ar -H stretching.

Major IR Bands of Compounds (83-91). Compound no. 3500-3000 cm-3 3000-2600 cm-3 2500-1500 cm-3 1500-1000 cm-3 1000-500 cm-3 (83) 3292.38 ….. 1653.12 1508.02 1338.08 1275.40 721.72 (84) 3336.74 3276.24 2978.55 2939.49 2850.97 1654.48 1637.22 1508.96 1475.77 1337.89 1208.97 1157.88 1045.25 941.05 780.99 720.19 (85) 3283.49 3141.22 2971.42 1655.20 1638.03 1592.62 1509.00 1337.72 1275.09 1189.79 1158.45 1120.42 1054.61 1013.96 828.52 774.49 720.75.

Compound no. 3500-3000 cm-3 3000-2600 cm-3 2500-1500 cm-3 1500-1000 cm-3 1000-500 cm-3 (86) 3295.77 3116.71 3032.00 2980.16 1654.53 1592.22 1518.27 1458.30 1337.10 1269.81 1115.36 1055.70 969.94 932.65 814.47 722.25 (87) 3278.68 2918.59 1656.04 1592.27 1514.64 1460.41 1421.46 1335.16 1276.97 1233.25 1054.83 939.54 775.58 720.98 (88) 3270.01 …. 1654.85 1592.42 1509.47 1335.73 1276.26 1232.95 1053.87 939.37 719.77.

Compound no. 3500-3000 cm-3 3000-2600 cm-3 2500-1500 cm-3 1500-1000 cm-3 1000-500 cm-3 (89) 3341.02 3270.02 2980.17 1654.53 1582.27 1517.22 1448.30 1327.10 1271.81 1125.36 824.52 784.49 720.75 (90) 3326.74 3282.24 2978.20 1634.03 1582.62 1529.00 1278.09 1192.69 1169.42 1130.22 942.01 770.89 722.39 (91) 3276 …. 1645.87 1589.32 1353.98 1243.33 970.23 788.21 712.35.

Conclusion.

Antiviral. Conclusion. Antifungal. Antimicrobial Antitumor Activities.

Future Work.

Chemistry can be divided into various sub-discipline but in the Lab on a day-to-day basis, it essentially boils down to three types of activity: making, modelling and measuring..

1. Světlik , J.V., L.; Mayer, T. U.; Catarinella , M. Bioorg . Med. Chem. Lett . 2010, 20, 4073–4076. doi:10.1016/j.bmcl.2010.05.085. 2. Hamama , W.S.W., M. A.; EL- Hawary , I. I.; Zoorob , H. H. J Heterocyclic Chem , in press. 3. Shin, K.D.L., M. Y.; Shin, D. S.; Lee, S.; Son, K. H.; Koh , S.; Paik, Y. K.; Kwon, B. M.; Han, D. C. J. Biol. Chem. 2005, 280, 41439. http://dx.doi.org/10.1074/jbc.M507209200 PMid:16234246. 4. Demers, J.H., W.; Johnson, S.; Klaubert , D.; Look, R.; Moore, J. Bioorg . Med. Chem. Lett . 1994, 4, 2451. http://dx.doi.org/10.1016/S0960-894X(01)80408-X. 5. Dömling , A.J.C.r ., Recent developments in isocyanide based multicomponent reactions in applied chemistry. 2006. 106(1): p. 17-89. 6. (a) Williams, R.M.C., R. J. Acc. Chem. Res. 2003, 36, 127; ( b) Dounay , A. B.; Overman , L. E. Chem. Rev. 2003, 103, 2945. 7. M. Afzal, G.A.-O., J. M. Al-Hassan, N. Muhammad, Heterocycles 1984, 22, 813–816. 8. M. E. Hanke and S. M. Talaat , T.b.a.p.o.h.L.a.i.u.a.a.r.f.i.a.f.R.S . 9. S. M. Talaat , H.f.i.m.B.M.J ., 944-945 (1960). 10. H. Chang and S. E. Suzuka , L.-O.-.- n.d.f.t.h.p.i.t.o.a.o.s.c.b.B.B . 11. Mustafa, S.M.N., V.A.; Chittoor , J.P.; Krishnapillai , S. Mini-Rev. Org. Chem. 2004, 1, 375–385..

THANK YOU.