one-pot synthesis of thiazole hydrazones in water

A total of eight thiazole hydrazone derivatives were successfully synthesized and characterized in this project. The structure of bagi lapan thiazole hydrazone derivati theyG-Fac-Ft 2018-0800.000000000000001-2017-2010-12-12-12-12-01-12-12-10-10-12-12-10-10-11-10-10-10-10-10-10-10-10-5 can't basis see CC-BY will be the structure of bagi lapan bagi lapan bagi lapan body bagi lapan body bagi lapan thiazole hydrazone derivati telah menggnakan IR, 1H NMR, 13C NMR, HMQC, HMBC and tool pengukur take lebur. This thesis entitled “SINGLE PATH SYNTHESIS OF THIAZOLE HYDRAZONE IN WATER” was prepared by TAN KIT LIN and submitted in partial fulfillment of the requirements for the Bachelor of Chemistry (Hons) at Universiti Tunku Abdul Rahman.

It is certified that TAN KIT LIN (ID No.: 15ADB07445) has completed this Final Year Project entitled "SYNTHESIS OF THIAZOLE HYDRAZONE IN WATER" under the supervision of Associate Professor Dr.

Introduction of thiazole hydrazones

As a result, the carbonyl oxygen will be replaced by the -NNH2 group contributed by the hydrazine molecule. Thiazolehydrazone compound can be easily synthesized via the condensation reaction between aromatic aldehydes or ketones and thiosemicarbazide. The intermediate product - thiosemicarbazone is obtained which subsequently reacts with the n-bromoacetophenone to give the final product which is thiazolehydrazone via Hantzsch cyclization reaction (Zhang et al., 2012).

Application of thiazole hydrazones

One pot synthesis

A one-pot approach can thus reduce chemical waste, save time and simplify practical aspects (Hayashi, 2016).

Distilled water as green solvent

Objectives

To synthesize a series of thiazole hydrazone derivatives using water as a solvent through one-pot synthesis. To study the effect of different solvents on product yield in one-pot synthesis. To characterize the structures of thiazole hydrazone derivatives using melting point apparatus, Fourier-Transform Infrared Spectroscopy (FTIR), Thin Layer Chromatography (TLC) and Nuclear Magnetic Resonance Spectroscopy (NMR).

One pot synthesis

Synthesis of new nitro-substituted thiazolyl hydrazone derivatives

First, 5-arylfurfural thiosemicarbazones were synthesized by reacting 5-arylfurfurals with thiosemicarbazide in 40 mL of ethanol and refluxed for about 12 h. Then, the 5-arylfurfural thiosemicarbazones were mixed with the 2-bromoacetophenone derivatives in 20 mL of ethanol and refluxed again for another 8 h. The 5-arylfurfural thiosemicarbazones then undergo ring closure and finally produced the new thiazolyl hydrazone derivatives.

According to Maillard et al. 2013), thiazole hydrazone derivatives can be easily synthesized via a two-step reaction. In the first step, a series of carbonyl compounds were reacted with thiosemicarbazide in ethanol under reflux condition. Subsequently, the intermediate thiosemicarbazone was obtained, which was then reacted with 2-chloro-1-(2-hydroxy-5-methoxyphenyl)-ethanone.

4'-(2-methylpropyl)acetophenone (0.01 mol), thiosemicarbazide (0.01 mol) and 1 ml of concentrated hydrochloric acid, HCl were mixed together in 15 ml of methanol. After refluxing the reaction for 2 h, the mixture was cooled to room temperature, leading to the formation of 1-(1-(4-isobutylphenyl)ethylidene)thiosemicarbazide as an intermediate. After that, the intermediate 1-(1-(4-isobutylphenyl)ethylidene)thiosemicarbazide was reacted with phenacyl bromide/substituted phenacyl bromide in 50 mL of isopropanol and refluxed for 2–4 h.

Subsequently, the crude product - 2-thiazolylhydrazones produced - was filtered and purification was performed using silica gel column chromatography (Anbazhagan and Sankaran, 2015).

Figure 2.6: Synthesis of 2-hydrazino-1,3-thiazole derivatives by Maillard et al

Synthesis of thiazolylhydrazone derivatives via one-pot multicomponent reaction

First, o-toluidine (1) was reacted with ammonium thiocyanate and the reaction mixture was refluxed at 100–110 °C for 8 h and allowed to evaporate below 50% of the total volume. 2-amino-4-methylbenzo[d]thiazole (3) will be formed and react with hydrazine hydrate under reflux for 4 hours while stirring. Acetone was then mixed with a solution of 2-hydrazine-4-methylbenzothiazole (4) in ethanol and 1 M hydrochloric acid and the reaction mixture was shaken for 15 minutes at room temperature.

The precipitate was finally filtered off and recrystallized from ethanol to give a good yield of 2-hydrazino-4-methylbenzo[d]thiazole as a white solid. Phenyl thiazole hydrazone can be readily synthesized by reacting equal molar amounts of 2-hydrazino-4-phenyl thiazole and appropriate aromatic aldehydes in absolute ethanol or methanol, followed by reflux for 3 h. In this reaction, acetic acid was added as a catalyst to obtain an ideal yield.

Pure thiazole hydrazone derivatives can be obtained by evaporating the excess solvent through vacuum and recrystallized from ethanol (Khan et al., 2015). 38 2.2.7 Synthesis of arylidene-hydrazinyl-thiazole derivatives. 2014) had successfully synthesized arylidene-hydrazinyl-thiazole derivatives by a suitable Hantzsch condensation reaction. In the presence of the solvent that is ethanol, a series of aromatic aldehydes were condensed with hydrazinecarbothioamides and followed by cyclization process with α-halocarbonyl derivatives produced arylidene-hydrazinyl-thiazole derivatives.

Figure 2.9: Synthesis of 2-Hydrazino-4-methylbenzo[d]thiazole by Weng, Tan and Liu (2012)

Synthesis of 4- H -Benzo[b]pyrans in water at ambient temperature In the study of Mosaddegh, Hassankhani and Mansouri (2010), a several

An effective and environmentally friendly one-pot method of pyrimido[4,5-b]quinoline derivatives has been developed using water as a green solvent. These properties make it both cost effective and environmentally friendly and therefore widely known as a green solvent (Tabatabaeian et al., 2014). The reaction was performed at different temperatures and using different solvents to find the optimal reaction condition.

Table 2.2: Influence of the solvents on the synthesis of pyrimido[4,5- b]quinolone

Synthesis of 2-amino-4,6-diphenylnicotinonitriles in water without catalyst

The chemicals used

Methodology

Synthesis of thiazole hydrazones derivatives through one-pot reaction 2 mmol of starting material were mixed in a 50 mL of round bottom flask
Infrared spectroscopy (IR)
Nuclear Magnetic Resonance (NMR)
Thin Layer Chromatography (TLC)
Melting point apparatus

The instruments including Stuart SMP10 melting point apparatus, Perkin-Elmer Spectrum RX1 FT-IR spectrophotometer and JEOL ECX-400 FT- NMR spectrometer are used in this project. In this project ethanol was chosen as solvent because it is volatile and does not react with the solute – desired compound. When infrared radiation is directed at a compound, the specific bonds in the compound will absorb the radiation at specific frequencies.

The model of instrument used in this project was Perkin-Elmer Spectrum RX1 FT-IR spectrophotometer. For the NMR sample preparation, the sample was first dissolved in deuterated solvents such as dimethyl sulfoxide (DMSO) or mixture of DMSO-d6 and acetone-d6 which depends on the sample solubility in specific solvent. Since the amount of solvent is greater than the sample being analyzed, it is necessary to ensure that the solvent does not dominate the spectra.

In this project, a JEOL ECX-400 FT-NMR spectrometer was implemented to acquire one- and two-dimensional NMR, including 1H NMR, 13C NMR, heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple bond coherence (HMBC). Thin layer chromatography (TLC) is a very common chromatographic technique used in synthetic chemistry to identify compounds, monitor reaction progress, and also determine compound purity. The surface of the TLC plate is coated with a polar absorbent, usually silica, which acts as the stationary phase. In this project, a 1:1 mixture of ethyl acetate and n-hexane acts as the mobile phase.

A small portion of the sample was dissolved in the mixture of ethanol and chloroform at 1:1 ratio and the sample was spotted on the base line of plate. The plate was left undisturbed in the chamber until the mobile phase reached 1 cm from the top. Melting point of a compound is determined using Stuart SMP10 melting point apparatus in this project.

A sharp melting range of one or two degrees can be obtained if the compound is pure. The melting range is defined as the temperature at which the sample begins to melt and the temperature at which the melting process ends. A capillary tube closed at one end containing a small portion of the sample was inserted into the melting point apparatus and heated.

Conclusion

Future perspective

Synthesis and in vitro evaluation of novel nitro-substituted thiazolylhydrazone derivatives as anti-andidal and anti-cancer agents. Syntheses, spectral characterization, single crystal X-ray diffraction and DFT computational studies of new thiazole derivatives. An efficient, simple and green Zn(Phen)2Cl2 complex-catalyzed synthesis of 4-H-benzo[b]pyrans in water at ambient temperature.

An efficient, multi-component, one-pot synthesis of polyhydroquinoline derivatives through a Hantzsch reaction catalyzed by gadolinium triflate. Ultrasound promoted an efficient method for the one-pot synthesis of 2-amino-4,6-diphenylnicotinonitriles in water: a rapid procedure without a catalyst.