Mohammed S. Al-Ajely and Aymen N. Yaseen IJSER

Transcription

1 . International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April Synthesis of oxobenzotriazino acetic, benzimidazolyl hydrazides and some their hydrazones Mohammed S. Al-Ajely and Aymen N. Yaseen Abstract -Hydrazides of oxobenzotriazine and benzimidiazole (4), (3) were synthesized from their corresponding esters (3), (2). Those two types of hydrazides were allowed to react with some substituted Benz aldehydes resulting into the formation of new hydrazone compounds (52), (48) respectively. The structure of the studied compounds were confirmed using IR,HNMR,3CNMR, mass and well discussed. Introduction Keywords- benzotriazino, benzimidzolyl, hydrazides, hydrazones There are numerous methods in the literature for the preparation of hydrazides, Such as carbodimide, N-Amination of amides, Nitrile hydrolysis and acylation of hydrazines []. The last one is the most popular methods for hydrazide synthesis. These hydrazide and their condensation products were stated to possess a wide range of biological activities [2]. Some of hydrazides and their analogous hydrazones are psychopharmacological agent, such as mono amino oxidase (MAO) inhibitor and serotrin antagonists [3] hydrazides were also used to prepare diazoles and oxadiazoles compounds [4-6] most of them are biologically active and found many applications in medical area [7] it is well known that hydrazides when allowed to react with aldehyde or lactones they will transformed into their corresponding hydrazones[8]. Hydrazone compounds due to their azomerhine group activity have drawn the attention of many researchers for the synthesis of numerous hydrazone compounds by the well-known hydrazinolysis method [, 2]. These hydrazones likewise corresponding hydrazides have proofed to have a wide range. Of pharmaceutical applications [36]. In this work we tried to prepare two types of new hydrazide and some new derivatives of their hydrazones in an attempt to study their biological effect which will be our next work. 2 Experimental All reagents and chemicals were from BHD and Sigma-Aldrich companies and used without further purification. Melting points were determined 3 with Electro thermal 93 melting point apparatus. Infrared spectra were recorded on a Perkin-Elmer 6 FTIR. P PH, P PC NMR spectra were recorded at 25 or 4 MHz on a Bruker AV4 model or Bruker AV25 model NMR instrument. Accurate masses were obtained using a Water-Micromass LCT electrospray mass spectrometer. All the measurements were performed at the Chemistry department, university of Sheffield, Sheffield, United Kingdom. Compound () was prepared according to the well-known procedure[7].compounds, were prepared following the elsewhere published procedure[8]and compound(2)was also prepared following the published one[9]p P Structures of these compounds were elucidated using IR, NMR and mass measurements Authors address: Chemistry department, College of Education, Mosul University, Mosul - Iraq 26

2 P,P International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April Synthesis of hydrazide compounds (4), (3) General procedure) A mixture of the ester (3) or (2) (.5 mol.), and hydrazine hydrate (8%), (. mol.) in ethanol (2 ml) were refluxed for 2 hours. Excess ethanol was evaporated under reduced pressure and the precipitate product was crystallized from ethanol. 2.2 Synthesis of hydrazone compounds (5-9), (48) (General procedure) Equimolar quantities of hydrazide (4) or (3) and substituted bezaldehyde in (25 ml) of absolute ethanol were refluxed for three hours. The reaction mixture was then cooled and the solid precipitated was recrystallized from ethanol physical and spectral data were illustrated in the following article: 3 Results and discussion Ethyl 2-(4-oxobenzo[d][,2,3]triazin-3(4H)-yl)acetate(3) Oil bp C, IR spectrum, υ, cm : 34 (Ar-CH str.), 2988 (Aliphatic-CH str.), 2 (N=N str.), 747 (C=O str.easter), 685 (C=O str. amide), 65, 488 (C=C str.), 436 (C-Hbend), 275 (C-N str.). High resolution mass spectrum (EI): Found: m\z [M], Calculated (4-oxobenzo[d][,2,3]triazin-3(4H)-yl)acetic hydrazide (4) This compound (mp p PC)was prepared by hydrazinolysis of compound(3) as shown in scheme() the elucidation of its structure comes from IR,NMR and mass.ir spectrum, υ, cmp P:339 (NH str.), 338 (Ar-CH str.), 2958 (aliphatic-ch str.), 263 (N=N str.), 678, 659 (C=O str.), 633, 446 (C=C str.), 375 (C-H bend), 336 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: 4.3 (2H, s, NHR2R), 5. (2H, s, CHR2R), (4H, m, Ar-CH),.4 (H, 3 s, NH). P PC NMR (DMSO-dR6R), δ, ppm: 5.3, 9.85, 24.96, 28.54, 33.5, 36., 44.27, 66.2, 7.3. High resolution mass spectrum (EI): Found: m/z 22.2 [M]P P, Calculated 22.2 Aryl-N-(4-oxo benzo[d][,2,3]triazin-3-(4h-yl) acetic hydrazones ( 5-9 ) These series of hydrazone compounds, were prepared from the reaction of compound(4)with some substituted benzaldehydes, Scheme ().These compounds were characterized by a combination of spectral methods IR,NMR and mass.ir indicate the presence of azomethine group(-ch=n-) 3 absorbed around 64cmP PHNMR also support this finding through the signal resonated around ppm whilep PCNMR showed signal resonating around ppm related to the azomethine carbon for the studied compounds. The details of spectral data were illustrated below: 3-nitrophenyl-N(4-oxobenzo[d][,2,3]triazino-3(4H)-yl)hydrazone (5) White solid,mp p PC,85%yield. IR spectrum, υ, cmp P:32 (NH str.), 362 (Ar-CH str.), 2962 (aliphatic-ch str.), 7, 665 (C=O str.), 65 (C=N str.), 6, 4 (C=C str.), 388 (C-H bend), 334 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: 5.7 (2H, s, CH), (8H, 3 m, Ar-CH), 8.6 (H, s, CH), 2. (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 5.89, 9.57, 2.67, 2.79, 24.78, 25.5, 28.64, 3.88, 33.59, 36.22, 42.8, 45.64, 48.74, 55.37, 63.77, High resolution mass spectrum (EI): Found: m/z 353. [M]P P, Calculated nitrophenyl-N(4-oxobenzo[d][,2,3]triazin-3(4H)-yl)hydrazone (6) Pale yellow solid,mp.4243p PC,7%yield. IR spectrum, υ, cmp P:3225 (NH str.), 38 (Ar-CH str.), 3 (aliphatic-ch str.), 74, 677 (C=O str.), 6 (C=N str.), 567, 44 (C=C str.), 356 (C-H bend), 339 (C-N str.). P PH NMR (DMSO-dR6 R), δ, ppm: 5.6 (2H, s, CH), (8H, m, Ar-CH), 8.5 (H, s, CH), 2.2 (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 5., 9.2, 9.58, 25.6, 28.53, 28.66, 28.98, 3.2, 33.73, 34.7, 36.24, 4.67, 44.3, 48.55, 55.38, High resolution mass spectrum (EI): Found: m/z 353. [M]P P, Calculated chlorophenyl-N(4-oxobenzo[d][,2,3]triazino-3(4H)-yl)hydrazone (7) Yellow solid,mp.3233p PC67%yield. IR spectrum, υ, cmp P:329 (NH str.), 364 (Ar-CH str.), 2957 (aliphatic-ch str.), 75, 673 (C=O str.), 6 (C=N str.), 597, 448 (C=C str.), 353 (C-H bend), 333 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: 5.6 (2H, s, CHR2R), (8H, m, Ar-CH), (H, s, CH), 2. (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm:54.99, 8.66, 9.28, 24.88, 25.66, 27.6, 29.88, 3.5, 33.2, 37.55, 43.4, 5.67, 6.25, High resolution mass spectrum (EI): Found: m/z [M]P P, Calculated hydroxyphenyl-N(4-oxobenzo[d][,2,3]triazino-3(4H)-yl)hydrazone(8) White solid,mp.9496p PC,72% yield.ir spectrum, υ, cmp P:322 (OH str.), 356 (NH str.), 35 (Ar-CH str.), 298 (aliphatic-ch str.),72, 672 (C=O str.), 654 (C=N str.),64, 446 (C=C str.), 35 (C-H bend), 332 (C-N str.). P PH NMR (DMSO-d R6R), δ, ppm: 5.6 (2H, s, CHR2R), (8H, m, Ar-CH), (H, s, CH),. (H, s, OH),.8 (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 53.68, 2.3, 22.6, 24.88, 25.87, 28.86, 3.6, 36., 43.24, 45.76, 49.27, 6.87, 7..High resolution mass spectrum (EI): Found: m/z [M]P P, Calculated methylphenyl-N(4-oxobenzo[d][,2,3]triazino-3(4H)-yl)hydrazone(9) Pale yellow solid,mp.22p PC. IR spectrum, υ, cmp P:382 (NH str.), 363 (Ar-CH str.), 2959 (aliphatic-ch str.),7, 667 (C=O str.),64 (C=N str.), 582, 46 (C=C str.),392 (C-H bend),332 (C-N str.). P PH NMR (DMSO-d R6R), δ, ppm: 5.6 (2H, s, CH), (8H, m, Ar- 26

3 International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April CH),(H, s, CH),.9 (H, s, NH). 3 C NMR (DMSO-d 6), δ, ppm: 2.5, 5.85, 9.58, 25.5, 27.6, 28.62, 29.9, 3.64, 33.67, 36.8, 4.4, 44.3, 45.5, 55.36, High resolution mass spectrum (EI): Found: m/z [M], Calculated Ethyl H-benzo[d]imidazole-2-carboxylate (2) This compound was prepared by the esterification of compound () with ethanol, mp C,8%yield.The IR spectrum, υ, cm : 3233 (NH str.), 354 (Ar-CH str.), 2992 (aliphatic-ch str.), 78 (C=O str.), 622 (C=N str.), 488 (C=C str.), 35 (C-N str.). H NMR (DMSO-d 6), δ, ppm:.3 (3H, t, CH 3), 4.4 (2H, q, CH 2), (4H, m, Ar-CH), 3.5 (H, s, NH). 3 C NMR (DMSO-d 6), δ, ppm: 2.5, 5.5, 25.5, 27.44, 27.6, 28.62, 3.64, 33.67, 4.4, High resolution mass spectrum (EI): Found: m/z 9.82 [M], Calculated

4 International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April

5 International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April H-benzo[d]imidazole-2-carbohydrazide (3) This hydrazide was also prepared by hydrazinolysis of compound (2).Melting point of this yellow solid compound C. The following spectral data support its formation, IR spectrum, υ, cm : 332, 3256 (NH str.), 364 (Ar-CH str.), 2967 (aliphatic-ch str.), 658 (C=O str.), 66 (C=N str.), 596, 474 (C=C str.), 323 (C-N str.). H NMR (DMSO-d 6), δ, ppm: 4.7 (H, s, NH), 6.9 (H, s, NH), (4H, m, Ar-CH), 2.3 (H, s, NH), 3.5 (H, s, NH). 3 C NMR (DMSO-d 6), δ, ppm: 24.96, 28.54, 33.5, 36., 4., 44.28, High resolution mass spectrum (EI): Found: m/z 77.7 [M], Calculated Syntheses of Aryl - N- Hbenz [d] imidazole -2-yl-hydrazone (48) The condensation os some substituted benzaldehydes with compound (3) resulted into the formation of the above compounds,scheme(2).the formation of azomethine group (-CH=N) comes from the study of IR,NMR and mass spectra.these studies supports its formation through IR which revealed the absence of the original C=O group absorption in amide. NMR showed CH- of azomethine group resonating at ppm and 3 CNMR of the carbon of this group at ppm.Details of their spectral data where illustrated below: 4-nitrophenyl-NH-benzo[d]imidazole-2-yl hydrazone(4) White solid,mp.3-32p PC,8% yield.ir spectrum, υ, cmp P: (NH str.), 39 (Ar-CH str.), 2967 (aliphatic-ch str.), 667 (C=O str.), 6 (C=N str.), 548 (asym. N-O), 446 (C=C str.), 344 (sym. N-O), 323 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: (8H, m, Ar-CH), 8.8 (H, s, 3 CH), 2.9 (H, s, NH) 3.6 (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 3.26, 2.72, 24.2, 25.54, 28.57, 3.28, 32.47, 4.78, 44.99, 45., 45.22, 49.5, 57.. High resolution mass spectrum (EI): Found: m/z 3.93 [M]P P, Calculated dimethylaminophenyl-NH-benzo[d]imidazole-2-yl hydrazone(5) Yellow solid,mp p PC75% yield.ir spectrum, υ, cmp P: 393 (NH str.), 322 (Ar-CH str.), 2886 (aliphatic-ch str.), 654 (C=O str.), 6 (C=N str.), 442 (C=C str.), 39 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: 3. (6H, s, (CHR3R)R2R), (8H, m, Ar-CH), 8.5 (H, s, CH), 2.2 (H, s, NH), (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 48.55, 4.25, 2.77, 23.54, 25.89, 3.77, 32.42, 33.4, 4.24, 42., 43.9, 44.7, 45.5, High resolution mass spectrum (EI): Found: m/z 38.5 [M]P P, Calculated chlorophenyl-NH-benzo[d]imidazole-2-yl hydrazone(6) Red solid,mp p PC,7% yield.ir spectrum, υ, cmp P: (NH str.), 39 (Ar-CH str.), 2967 (aliphatic-ch str.), 667 (C=O str.), 6 (C=N str.), 548 (asym. N-O), 446 (C=C str.), 344 (sym. N-O), 323 (C-N str.). P PH NMR (DMSO-dR6R), δ, ppm: (8H, m, Ar-CH), 8.8 (H, s, CH), (H, s, NH), 3.6 (H, s, NH).P PC NMR (DMSO-dR6R), δ, ppm: 5.57, 2.44, 25.87, 27.47, 33.45, 33.54, 36.89, 43.56, 44.97, 45.3, High resolution mass spectrum (EI): Found: m/z 3.9 [M]P P, Calculated ,6-dichlorophenyl-NH-benzo[d]imidazole-2-yl hydrazone(7) White solid,mp p PC,85%yield. IR spectrum, υ, cmp P: (NH str.), 357 (Ar-CH str.), 292 (aliphatic-ch str.), 684 (C=O str.), 69 (C=N str.), 442 (C=C str.), 34 (C-N str.), (C-Cl str.). P PH NMR (DMSO-dR6R), δ, ppm: (7H, m, Ar-CH), 8.8 (H, s, CH), 2.9 (H, s, 3 NH), 3.6 (H, s, NH). P PC NMR (DMSO-dR6R), δ, ppm: 3.7, 2.54, 23.37, 25.9, 29.54, 3.5, 3.85, 34.42, 35.4, 42.99, 44.89, 45.35, 56.. High resolution mass spectrum (EI): Found: m/z [M]P P, Calculated methoxyphenyl-NH-benzo[d]imidazole-2-yl hydrazone(8) White solid,mp.28-28p PC65% yioeld.ir spectrum, υ, cmp P: 32 (NH str.), 397 (Ar-CH str.), 298 (aliphatic-ch str.), 664 (C=O str.), 6 (C=N str.), 446 (C=C str.), 323 (C-N str.), 248 (asym. O-CHR3R), 26 (sym. O-CHR3R). P PH NMR (DMSO-dR6R), δ, ppm: 3.8 (3H, s, CHR3R), (8H, m, Ar- 3 CH), 8.6 (H, s, CH), 2.4 (H, s, NH), 3.5 (H, s, NH). P PC NMR (DMSO-dR6R), δ, ppm: 55.7, 3.8, 4.84, 2.4, 23.24, 24.87, 27.22, 29.37, 34.99, 43., 45.3, 49.72, 55.6, High resolution mass spectrum (EI): Found: m/z 295.9[M]P P, Calculated Acknowledgments The authors would like to thank the department of chemistry of Sheffield university for their cooperation of providing the facility to do the spectral measurements and hosting Ayman for more than 9 months as a research scholar in UK. We also appreciate the iraqi ministry of higher education and research for their offer this fellowship to Ayman. 26

6 International Journal of Scientific & Engineering Research, Volume 7, Issue 4, April References [] H.Pausen and D.stoye The chemistry of hydrazides John Wiley and Songs, 55,97. [2] S. Rollas, N. Gulerman, and H. Erdeniz, Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3- acetyl-2,5-disubstituted,3,4-oxadiazolines, Farmaco, 57, No.2, 7 74,22. [3] F. R. Pavan, P. I. da S. Maia, S. R. A. Leite, V. M. Deflon, A. A. Batista, D. N. Sato, S. G. Franzblau, and C. Q. F. Leite, Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti - Mycobacterium tuberculosis activity and cytotoxicity, Eur. J. Med. Chem., 45, No.5, , 2. [4] H. Hanumanagoud and K. M. Basavaraja, Synthesis and biological evaluation of some new oxadiazole and pyrazole derivatives incorporating benzofuran moiety, Der Pharma Chem., vol. 5, No. 4, 87 98, 23. [5] F. A. Yassin and A. F. Seleim, Synthesis and reactions of oxadiazolo, thiadiazolo and triazolo phthalazin- ( 2 H ) -one derivatives, Der Pharma Chem., vol. 4, No. 3, , 22. [6] A. R. Saundane and Y. Manjunatha, Synthesis, antimicrobial and antioxidant activities of 2-oxo-6-phenyl-2-yl-4-(2 -phenyl-5 -substituted H-indol- 3 -yl),2-dihydro pyridin-3-carbonitriles and their derivatives, Arab. J. Chem. 2. [7] Z.Qin chapo.j.and Z. Yizhany, J. chinese chem.soc,5, 443, 24. [8] M. Freifelder, J. Org. Chem., 3, 3875, 966. [9] T. Govindasami, Synthesis, Characterization and Antibacterial Activity of Biologically Important Vanillin Related Hydrazone Derivatives, Int. J. Org. Chem., vol., No. 9,. 7 77, 2. [] A. Özdemir, G. Turan-Zitouni, Z. A. Kaplancikli, and M. D. Altintop, The synthesis of some new hydrazone derivatives containing the benzothiazole moiety, J. Serbian Chem. Soc., vol. 77, No. 2, pp. 4 46, 22. [] J.Zabicky, The chemistry of amides John wiley and Sons Ltd,97. [2] T. Govindasami, Synthesis, Characterization and Antibacterial Activity of Biologically Important Vanillin Related Hydrazone Derivatives, Int. J. Org. Chem.,,No , 2. [3] R. F. Smith, A. C. Bates, A. J. Battisti, P. G. Byrnes, C. T. Mroz, T. J. Smearing, and F. X. Albrecht, Reactions of hydrazines with esters and carboxylic acids, J. Org. Chem., vol. 33, No. 2, , 968. [4] P. A. S. Smith, The Curtius Reaction, in Organic Reactions, John Wiley & Sons, Inc.,24. [5] W. F. Short, J. Chem. Soc., 2, 445,92. [6] T. Sheradsky, A new method for the amination of anionic nitrogens, Tetrahedron Lett., vol. 9, No. 6, 99 9, 968. [7] P. Wiklund and J. Bergman, The Chemistry of Anthranilic Acid, Current Organic Synthesis, vol. 3, No , 26. [8] P. A. Thakurdesai, S. G. Wadodkar, and C. T. Chopade, Synthesis and anti-inflammatory activity of some benzimidazole-2-carboxylic acids, Pharmacologyonline, vol., , 27. [9] R. M. Silvertein, G. C. Bassler and T. C. Morrill, Spectrometric identification of Organic Compounds, 3rd Ed., John Wiley and Sons, Inc, New York,,