Synthesis, Characterization of New Hydrazone Derivatives Containing Heterocyclic Meioty Ahmed A

Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Synthesis, Characterization of new Hydrazone derivatives containing heterocyclic meioty Ahmed A. Saheeb1 and Wasan k.Damdoom2 1Col. of Agric. , University of Summer , Iraq. 2Col. of pharmacy, National of Science and Technology, Thi-Qar, Iraq.

*Corresponding author: [email protected], [email protected] ( Damdoom)

Abstract The present work includes synthesis and characterization of new hydrazine, compound (F1) derived from ethyl benzoate. Firstly, benzoate hydrazide [A1] has been synthesized from the condensation of ethyl benzoate with hydrazine. Then the benzoate hydrazide was reacted with phenylisothiocynate to prepare [B1]. Cyclization reaction of product [B1] with sodium hydroxide produced terazole derivative [C1].On the other hand, alkylation reaction of compound [C1] with chloroethylacetate in the presence of Sodium acetatetrihydrate as a catalyst resulted [D]. The acid hydrazide derivative [E1] has been synthesized by the reaction of compound [D1] with hydrazine hydrate. Finally, hydrazone derived [F1] was synthesized by the condensation reaction of the acid hydrazide [E1] with isatin. The synthesized compound was characterized by, FT-IR, 1H-NMR, 13C-NMR and Mass spectra. Compound (F2) derived from Methyl-4-hydroxybenzoate react with ethylchloroacetate ton prepare (A2) this compound react with hydrazine by reflux and used ethanol as as asolvent to give (B2). The hyrazone [C2] was synthesized by the condensation of 4-(2-hydrazino-2-oxoethoxy) benzohydrazide, and add 5 drops of acetic acid. Then the mixture refluxed for 8 hours (monitored by TLC). The hydrazone was precipitated, filtered and recrystallized from ethanol) to get white solid. The synthesized compounds were characterized by, FT-IR, 1H-NMR, 13C-NMR .

Keywords: Hydrazones, benzoate, FT-IR How to cite this article: Saheeb AA, Damdoom WK (2020): Synthesis and characterization of new hydrazone derivatives containing heterocyclic meioty, Ann Trop Med & Public Health; 23(S16): SP231620. DOI: http://doi.org/10.36295/ASRO.2020.231620

Introduction Hydrazones are a class of azomethine has the group -C=N-N-obtained by the reaction of hydrazide with aldehydes or ketones .Hydrazides have the general formula of NH2-NH-R which derived from hydrazine NH2-NH2

(El-Wahab, et al., 2015). A hydrazone is the functional group with structure R1R2C=NNH2. They are like aldehydes or ketones, with an NNH2 group instead of the oxygen atom. They are made by reacting hydrazines with ketones or aldehydes (Abdel-Galil et al., 2018).

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Hydrazones are very useful molecules to do some reactions. For example, a ketone can be reduced down completely if made into a hydrazine and then treated with sodium ethoxide (Wolff–Kishner reduction). Hydrazones are very important intermediates in many reactions, such as the Fischer indole synthesis. This makes indoles, groups which are found in many drugs (Bingul et al., 2016). Hydrazones contain two nitrogen atoms of different nature connected with each other. The carbon nitrogen double bond (C=N) that is conjugated with a lone pair of electrons on the terminal nitrogen atom (N̈ ) these structural fragments are responsible for the physical and chemical properties of hydrazones. Both nitrogen atoms of the hydrazone group are nucleophilic, but the amino nitrogen is more active.The carbon atom of hydrazone group has both electrophilic and nucleophilic characteristics (Kamal, et al., 2015; Sayed et al., 2018). Hydrazone formation is extensively used in the detection, determination and isolation of compounds containing carbonyl group (Can et al., 2017) Talanta. Photometric methods for determining aldehydes and ketones are based on their reaction with 2,4dinitrophenylhydrazine to form corresponding hydrazones. The formation of aromatic hydrazone derivatives is used to measure the concentration of low molecular weight aldehydes and ketones, e.g. in gas streams. For example, dinitrophenylhydrazine coated onto a silica sorbent is the basis of an adsorption cartridge. The hydrazones are then eluted and analyzed by HPLC using a UV detector. The compound carbonyl cyanid trifluoromethoxyphenylhydrazone (abbreviated as FCCP) is used to uncouple ATP synthesis and reduction of oxygen in oxidative phosphorylation in molecular biology. Phenylhydrazine reacts with glucose to form an osazone (Day, A. C.; Whiting, M. C. (1970) .

2. Materials and methods

2.1. Reagents

All the chemicals and solvents used were of chemically pure grade, and commercially available.

2.2 Apparatus

Melting points of all the prepared compounds were observed in an electro thermal melting point apparatus model (Melting SMP31). The FTIR spectra in the range of (400-4000) cm-1 were recorded as KBr disc by the use of a perkin Elme,tensor 27 (Bruker). Nuclear Magnetic Resonance Spectra were obtained using Burker DXR System AL 500(500 MHz). Mass Spectra were obtained utilising (Network Mass Selective Detector 5973).

2.3. Synthesis of compounds

2.3.1 Synthesis of compounds {[A1] [B1] [C1] [D1] [E1]} [(Redha et al., 2014).], [Yasmin K,(2017)].

The titled compounds were synthesized according to literatures 2.3.2. Synthesis of (Z)-2-((4,5-diphenyl-4H-1,2,4-triazol-3-yl)thio)-N'-(2-oxoindolin-3-ylidene)acetohydrazide [F1]

The hyrazone [F1] was synthesized by the condensation of 2-[(4,5-diphenyl-4H-1,2,4-triazol-3- yl)thio]acetohydrazide) [A1] (0.4 gm ,0.0012mol) and 1H-indole-2,3-dione (0.176 gm, 0.0012mol) in ethanol (30

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

ml), and add 5 drops of acetic acid. Then the mixture refluxed for 4 hours (monitored by TLC). The hydrazone was precipitated, filtered and recrystallized from ethanol to get orange solid, melting point 254-257 °C, yield 90%.

S H H O O O N O Ph NH N 2 N NH Hydrazine hydrate 99% H PhNCS ethanol , reflux ethanol , reflux

methyl benzoate benzohydrazide 2-benzoyl-N-phenylhydrazinecarbothioamide [A1] [B1]

ethanol , reflux NaOH 4N,2ml

O N N O O N N S N O N SH NaOAC.3H2O Cl Ethanol ethyl chloroacetate S-4,5-diphenyl-4H -1,2,4-triazol-3-yl O-ethyl carbonothioate 4,5-diphenyl-4H-1,2,4-triazole-3-thiol [D1] [C1] ethanol , reflux Hydrazine hydrate 99%

H N N N O NH2 C N O

O N H

4,5-diphenyl-4H -1,2,4-triazole-3- indoline-2,3-dione carbohydrazide [E1]

ref lux ,G,A,A ethanol ,

N N H N N C N O H2O Scheme 1. SynthesisN of (F1) O H N '-(2-oxoindolin-3-ylidene)-4,5-diphenyl-4 H-1,2,4-triazole-3-carbohydrazide

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

2.3. 3. Synthesis of compounds {[A2] [B2] [C2] [(Athraa et al., 2019).

The titled compounds were synthesized according to literatures

2.4.. Synthesis of N'-[(1E)-2-furylmethylene]-4-{2-[(2E)-2-(2-furylmethylene)hydrazino]-2- oxoethoxy}benzohydrazide [F2] .The hyrazone [F2] was synthesized by the condensation of 4-(2-hydrazino-2- oxoethoxy)benzohydrazide (0.224 gm ,0.001mol) and furfural (0.192 gm, 0.002mol) in ethanol (30 ml), and add 5 drops of acetic acid. Then the mixture refluxed for 8 hours (monitored by TLC). The hydrazone was precipitated, filtered and recrystallized from ethanol to get white solid, melting point 214-216 °C, yield 71%.

O O O O O HO O K Co 2 3 O O Cl dry aceton O ethyl 4-hydroxybenzoate ethyl chloroacetate ethyl 4-(2-ethoxy-2-oxoethoxy)benzoate [A2]

Ethanol Hydrazine hydrate 99% reflux

NH O O H 2 HN O 2 O O NH O NH2 2-Forfaldehyde 2-(4-(hydrazinyloxycarbonyl)phenoxy)acetohydrazide

B2

O N O

HN O O O NH

O [F2] N

(Z)-N '-(furan-2-ylmethylene)-2-(4-(((Z)-2-(furan-2- ylmethylene)hydrazinyloxy)carbonyl)phenoxy)acetohydrazide Scheme2. Synthesis of compound (F2)

3. Result and Discussion 3.1. Physical properties

The physical properties of the prepared compounds [F1,F2] are shown in Table1 .

Table1: physical properties data of the compounds [F1,F2]

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Molecular NO. Yield% Colour Rec.Solvent formula M .P ˚C Rf M.wt

254-257 0.72 454 F 1 F1 C24H18N6O2S 74.8 orange Ethanol

214-216 0.9 380 F2 C19H16N4O5 71 White Ethanol

3.2. FT-IR spectra

The FTIR spectrum (KBr ,υ, cm−1) for F1 compound shows a characteristic stretching absorption bands at 3216cm-1, 3187 cm-1, 3067cm-1,2 925 cm-1, 1679cm-1,1712, 1620 cm-1assigned to υ(NH), υ(N-H)ring ,υ(C=C aromatic), υ (C-H alphatic), υ(C=O)amid , υ(C=O)ring,υ(C=N) of azomethine respectively. And the compound F2 a characteristic stretching absorption bands at 3218cm-1, , 3050cm-1, 3024cm-1, 1649cm-1, 1605 cm-1assigned to υ(NH), υ(C=C aromatic), υ (C-H alphatic), υ(C=O) , υ(C=N) of azomethine respectively

Figure1: IR spectrum of F1 Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231620

Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Figure2: IR spectrum of F2

3.3. Nuclear Magnetic Resonance Spectra (1H-NMR) The 1H-NMR spectrum of F2 in DMSO-d6 and the chemical shifts (δ) were calculated in ppm downfield form

TMS (tetamethylsilane) showed the following signals , singlet at 5.17 ppm refer to –OCH2CO- methylene protons also singlet signal at 4.76 ppm for amide proton (NH) whearas anther multiplet signal at (6.64 -7.92) ppm for aromatic protons and signal at (8.23,8.28) ppm for azomethine protons and signal broad peak at δ 11.60 ppm for hydroxyl totomarianism, as shown in Figure (4).

3.3 Nuclear Magnetic Resonance Spectra (13C-NMR) The 13C-NMR spectrum in DMSO-d6 of compound (F2) shows the following signals signal at 65 ppm due to carbon atom of the (-CH2-) group and another signals at δ (112.6 -145.4 ppm) indicated to aromatic carbons in the phenyl ring and five ring.Beside that the signals at (145,149.4 ppm refer to (C=N) and signal at δ (164.4,168.6 ppm) for carbon atoms of amid group (O=C-NH), as shown in Figure(5).

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Figure 5 : 13C- NMR analysis for F2

3.4 Mass Spectra of Compounds

The mass spectra of (F1) appears molecular ion peak at 454 m/z which is in conformity with the molecular formula

C24H18 N6O2S, other peaks m/z (384,294,253,234,180,158 ,131 ,104 ,77 ,51) as shown in Figure (5).and the compound mass spectra of (F2) appears molecular ion peak at 380 m/z which is in conformity with the molecular formula C19H16N4O5, other peaks m/z (287,271,213,178,151 ,121 ,104 ,81 ,52) as shown in Figure (6)

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Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16

Figure 6 :Mass spectrum of F1

Figure 7 :Mass spectrum of F2

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