WO2016111658A1 - Synthesis of thiosemicarbazone derivatives comprising sulphonamide group with potential anticonvulsant activity - Google Patents

Abstract

The present invention relates to the synthesis method of thiosemicarbazone derivatives comprising sulphonamide group and having high anticonvulsant/antiepileptic activity.

Description

DESCRIPTION

SYNTHESIS OF THIOSEMICARBAZONE DERIVATIVES COMPRISING SULPHONAMIDE GROUP WITH POTENTIAL ANTICONVULSANT ACTIVITY

Subject of the Invention

The present invention relates to the synthesis method of thiosemicarbazone derivatives comprising sulphonamide group with high anticonvulsant activity.

State of the Art

Product development is continuously made in clinical applications in order to reduce the side effects and toxicity of drugs used in treatment of various diseases and to ensure that the drugs show their effect in short time during the course of the treatment. Moreover, new drugs are required to be developed, since some drugs are dropped out of use in time due to not being suitable for health.

Epilepsy disease, which is also commonly called as "sara" is hard to treat and negatively affects the daily life of patients. In this disease, abnormal electricity is temporary spread in the brain cells of patients. Therefore, conscious, behavioural, emotional, mobile, or sensory functional disorder is seen in patients. Anti-epileptic (anticonvulsant) drugs are used in treatment of this disease. In the prior art, drugs with the active ingredients of phenytoin, phenobarbital , carbamazepine, sodium valproate are used. These drugs are generally preferred in epilepsy treatment, since the drugs comprising these active ingredients are inexpensive, have long time usage experience, and their adverse effects are known better. However, these drugs may interact with other drugs used by the patient and may cause adverse effects especially on women, children, and elders. Also, drug resistance can be seen in some patients and patients may have a seizure even if they use the drug.

Patent No. 2012/04327 can be given as an example to the known status of the art. In this invention, use of a pharmaceutical composition comprising an anti- epileptic/anticonvulsant active ingredient and/or its pharmaceutically acceptable salts, hydrates, isomers, and polymorphs for additional treatment of partial convulsion with or without concomitant peripheral type neuropathic pain and secondary generalized convulsion is disclosed. However, said antiepileptic active ingredient does not have a characteristic that treats the patient and prevents the patient from having a seizure. In this case, only the pain of the patient can be treated, but the patient cannot be prevented from having a seizure.

In order to eliminate the above disclosed drawbacks, compounds, which have high anticonvulsant activity and low adverse effects, does not interact with other drugs used by the patient, and have high potential for use as active ingredient in anti-epileptic/anticonvulsant drugs.

Detailed Description of the Invention

The present invention relates to the synthesis method of thiosemicarbazone derivatives comprising sulphonamide group with high anticonvulsant activity.

In general terms, said synthesis method can be described as follows .

1^st Synthesis: 4-acetylbenzene is reacted with sulphonylchloride aniline and methoxyaniline at room temperature in the presence of dichloromethane, and sulphonamide derivative is obtained.

2^nd Synthesis: 4-substitutedphenyl isothiocyanade derivatives are converted into thiosemicarbazide derivatives by hydrazine monohydrate at room temperature, in the presence of diethylether .

3^rd Synthesis: The sulphonamide derivative obtained in the first step and the thiosemicarbazide derivative obtained in the second step are reacted during heating in the presence of methyl alcohol. As a result of this reaction, thiosemicarbazone derivatives comprising sulphonamide groups are obtained.

Detailed description of the above disclosed synthesis method is given below.

1^st Synthesis:

- 1.17 mmol 4-substituted aniline derivative is dissolved in 10 mL dichloromethane.

1.06 mmol triethylamine and 1-3 drops of pyridine are added into this mixture as catalysts.

- this mixture is mixed at room temperature for 15 minutes. Said room temperature corresponds to 25°C in chemical literature .

- 1.06 mmol of 4-acetylbenzenesulphonylchloride is dissolved in 5 mL of dichloromethane in a separate place and then added dropwise onto the above prepared mixture.

- during and/or after the addition, the mixture is heated in a heater system that has a condenser.

- the reaction mixture is cooled to room temperature when it is determined that the starting material found in the reaction mixture is completely used up.

- the cooled mixture is extracted with 2 M HC1. - organic phases are dried with sodium sulphate following extraction operation.

- the crystals formed as a result of the drying operation are washed with petroleum ether.

2^nd Synthesis:

- 1 mmol substituted isothiocyanade derivative is dissolved in diethylether.

- 1 mmol hydrazine monohydrate dissolved in diethylether is added dropwise into this mixture; Solid substances start to settle at the bottom of the mixture during additional processing .

- the solid substances settling at the bottom of the mixture are taken from the mixture vessel.

- solid substances are washed with water and diethylether.

- this solid substance is crystallized in a solvent.

3^rd Synthesis:

- 1 mmol of thiosemicarbazide derivatives are dissolved in heated 5 mL methanol.

- 1 mmol of substituted sulphonamide derivatives dissolved in 10 mL methanol are added onto this mixture.

- This reaction mixture is heated in a heater system that has a condenser for 48 hours.

- the reaction mixture is cooled down to room temperature when it is determined that the starting material found in the reaction mixture is completely used up.

- the solid substance formed following cooling operation is taken from the mixture.

- this solid substance is crystallized in a solvent.

In the first synthesis of the method according to the invention, the sulphonyl chloride group found in the structure of the 4-acetylbenzene sulphonyl chloride compound that is selected as the starting material is reacted with aniline and 4-methoxy aniline to obtain Compound 1 and Compound 2 derivatives of sulphonamide . Based on the method disclosed in the second synthesis, isothiocyanades carrying different substituents are treated with hydrazine monohydrate and thiosemicarbazide derivatives are obtained. The thiosemicarbazide derivatives obtained in the second synthesis and the sulphonamide derivatives obtained in the first synthesis (Compound 1 and Compound 2) are reacted to synthesize a total of 16 thiosemicarbazone derivatives carrying sulphonamide groups. The method of obtaining these synthesized compounds and their analysis results are given below .

Findings :

• Synthesis and analysis results of Compound 1 (4-acetyl- N-phenylbenzenesulphonamide ) : The values arranged by taking the multiples of the mole numbers disclosed in the above given first synthesis are provided below.

Compound 1 is synthesized according to the method disclosed in the first synthesis by using 3.4 grams (12.0 mmols) of 4- acetylbenzenesulphonylchloride and 1.23 grams (13.2 mmols) of aniline.

Obtaining efficiency of Compound 1 at the end of the synthesis is 44%. That is to say, about 1.5 grams of

Compound 1 is obtained.

Melting point of Compound 1 is about 83-84 °C. Compound 1 is an orange coloured substance in powder form.

Compound 1 is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate. However, it is insoluble in distilled water.

Molecular weight of Compound 1 is 275.32 g/mol.

Molecular formula of Compound 1 is C₁₄H₁₃NO₃S, and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 1 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 1.

FT-IR analysis results for Compound 1 are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

Table 2 : FT-IR analysis results for Compound 1. H NMR results for Compound 1 are given in the following pages .

• (4-acetyl-N- ( 4-methoxyphenyl ) benzenesulphonamide )

synthesis and analysis results for Compound 2:

Compound 2 is synthesized according to the method disclosed in the first synthesis by using 3.5 grams (11 mmols) of 4- acetylbenzenesulphonylchloride and 1.21 grams (13 mmols) of 4-methoxyaniline .

The efficiency of Compound 2 at the end of the synthesis is 43%. That is to say, about 1.5 grams of Compound 2 is obtained .

Melting point of Compound 2 is about 114-115°C.

Compound 2 is a brown substance in powder form.

Compound 2 is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, However, it is insoluble in distilled water.

Molecular weight of Compound 2 is 305.84 g/mol.

Molecular formula of Compound 2 is C₁₅H₁₅NO₄S, and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Theoretical Calculation Elemental Analysis Results Results (%) (%)

c 53.00 53.24

H 4.95 5.10 N 4.59 4.41

S 15.60 15.70

Table 3 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2. FT-IR analysis results for Compound 2 are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

Table : FT-IR analysis results for Compound 2.

H NMR results for Compound 2 are given in the following pages.

• (N-cyclohexyl-2- { 1- [ 4 -phenyl sulphamoyl

phenyl ] ethylidene } hydrazine carbothioamide ) synthesis and analysis results for Compound la:

0.58 mmol (0.16 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.58 mmol (0.1 gram) of N- cyclohexylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound la. This solid substance is crystallized by filtering and washing with ether. Obtaining efficiency of Compound la at the end of the synthesis is 92%.

Melting point of Compound la is about 228-230°C. Compound la is yellow.

Compound la is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , heated chloroform, and heated ethyl acetate. However, it is insoluble in distilled water.

Molecular weight of Compound la is 430.59 g/mol.

Molecular formula of Compound la is C21H26 4O2 S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 5 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound la.

FT-IR analysis results for Compound la are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band) (Bending band)

Table 6 : FT-IR analysis results for Compound la.

H NMR results for Compound la are given in the following pages .

• Synthesis and analysis results for Compound lb (N- phenyl-2- { 1- [ 4-phenylsulphamoylphenyl ]

ethylidene } hydrazine carbothioamide ) :

0.59 mmol (0.17 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.59 mmol (0.1 gram) of N- phenylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound lb. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound lb at the end of the synthesis is 92%.

Melting point of Compound lb is about 182-184°C.

Compound lb is yellow. Compound lb is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , and chloroform. However, it is insoluble in distilled water and ethyl acetate. Molecular weight of Compound lb is 424.54 g/mol.

Molecular formula of Compound lb is C21H20N4O2 S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 7 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound lb. FT-IR analysis results for Compound lb are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 8 : FT-IR analysis results for Compound lb.

H NMR results for Compound lb are given in the following pages .

• Synthesis and analysis results for Compound lc (N-(4- bromophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.41 mmol (0.11 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.41 mmol (0.1 kg) of N-(4- bromophenyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound lc. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound lc at the end of the synthesis is 72%.

Melting point of Compound lc is about 212-214°C. Compound lc is yellow.

Compound lc is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) . However, it is insoluble in chloroform, ethyl acetate, and distilled water.

Molecular weight of Compound lc is 503.44 g/mol. Molecular formula of Compound lc is C2iHigBrN402S2, and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 9 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound lc.

FT-IR analysis results for Compound lc are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

H NMR results for Compound lc are given in the following pages. • Synthesis and analysis results for Compound Id (N-(4- chlorophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) :

0.50 mmol (0.14 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.50 mmol (0.1 gram) of N-(4- chlorophenyl ) hydrazine carbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound lc. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound Id at the end of the synthesis is 68%.

Melting point of Compound Id is about 213-215°C. Compound Id is yellow.

Compound Id is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) . However, it is insoluble in chloroform, ethyl acetate, and distilled water.

Molecular weight of Compound Id is 458.98 g/mol.

Molecular formula of Compound Id is C21H1₉C IN4O2 S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

H 4.17 4.18

N 12.21 12.53

S 13.97 13.32

Table 11: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound Id. FT-IR analysis results for Compound Id are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

H NMR results for Compound ld are given in the following pages .

• Synthesis and analysis results for Compound le (N-(4- methoxyphenyl ) -2- { 1- [ 4-

(phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) :

0.52 mmol (0.14 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.52 mmol (0.1 gram) of N-(4- methoxyphenyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound le. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound le at the end of the synthesis is 56%.

Melting point of Compound le is about 195-197°C. Compound le is light pink.

Compound le is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, However, it is insoluble in distilled water.

Molecular weight of Compound le is 454.57 g/mol.

Molecular formula of Compound le is C22H22N4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 13: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound le. FT-IR analysis results for Compound le are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

H NMR results for Compound le are given in the following pages .

• Synthesis and analysis results for Compound If (N-(4- methylthiophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) :

0.47 mmol (0.13 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.47 mmol (0.1 gram) of N-[4- (methylsulphanyl ) phenyl ] hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound If. This solid substance is crystallized by filtering and washing with ether. Obtaining efficiency of Compound If at the end of the synthesis is 67%.

Melting point of Compound If is about 176-178°C. Compound If is yellow.

Compound If is soluble in acetone, heated methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, However, it is insoluble in distilled water.

Molecular weight of Compound If is 470.54 g/mol.

Molecular formula of Compound If is C22H22 4O2 S 3 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 15: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound If.

FT-IR analysis results for Compound If are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band) N-H s.b. S=0 C=N, N-H (b.b. ) ; C=S, as . s . b . imine Aromatic Thioamide and S=0 s.b. ring C=C (s.b.) s . s . b . (s.b.)

3279 1346, 1583 1495, 1518 1200

1156

Table 16: FT-IR analysis results for Compound ^'. Lf .

H NMR results for Compound lf are given in the following pages .

• Synthesis and analysis results for Compound lg (N- (benzyl) -2-{l- [4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) :

0.55 mmol (0.15 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.55 mmol (0.1 gram) of N- benzylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound lg. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound lg at the end of the synthesis is 45%.

Melting point of Compound lg is about 183-185°C.

Compound lg is yellow. Compound lg is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) . However, it is insoluble in chloroform, ethyl acetate, and distilled water. Molecular weight of Compound lg is 438.57 g/mol.

Molecular formula of Compound lg is C22H22N4O2 S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 17: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound lg. FT-IR analysis results for Compound lg are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

3250, 3141 1162

Table 18: FT-IR analysis results for Compound ^'. Lg.

H NMR results for Compound lg are given in the following pages .

• Synthesis and analysis results for Compound lh (N- (2- phenylethyl) -2-{l- [4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) :

0.51 mmol (0.14 gram) of 4-acetyl-N- phenylbenzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.51 mmol (0.1 gram) of N- (2- phenylethyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound lh. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound lh at the end of the synthesis is 84%.

Melting point of Compound lh is about 195-197°C. Compound lh is yellow.

Compound lh is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) . However, it is insoluble in chloroform, ethyl acetate, and distilled water.

Molecular weight of Compound lh is 452.57 g/mol. Molecular formula of Compound lh is C23H24N4O2 S2

theoretically calculated ingredient percentages

elemental analysis results are as follows.

Table 19: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound lh.

FT-IR analysis results for Compound lh are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

H NMR results for Compound lh are given in the following pages.

• Synthesis and analysis results for Compound 2a (N- (cyclohexyl) -2-{l- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.58 mmol (0.17 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.58 mmol (0.1 gram) of N- cyclohexylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2a. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2a at the end of the synthesis is 47%.

Melting point of Compound 2a is about 220-221°C. Compound 2a is yellow.

Compound 2a is soluble in acetone, heated methanol, chloroform, and dimethyl sulphoxide (DMSO) . However, it is insoluble in ethyl acetate and distilled water.

Molecular weight of Compound 2a is 460.59 g/mol.

Molecular formula of Compound 2a is C22H28 4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

13.92 13.82

Table 21: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2a.

FT-IR analysis results for Compound 2a are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 22 : FT-IR analysis results for Compound results for Compound 2a are given in the following

• Synthesis and analysis results for Compound 2b (N- (phenyl) -2-{l- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.6 mmol (0.18 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.6 mmol (0.1 gram) of N- phenylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2b. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2b at the end of the synthesis is 24%.

Melting point of Compound 2b is about 190-191°C. Compound 2b is white.

Compound 2b is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) . However, it is insoluble in distilled water.

Molecular weight of Compound 2b is 454.81 g/mol.

Molecular formula of Compound 2b is C22H21N4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 23: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2b.

FT-IR analysis results for Compound 2b are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 2 : FT-IR analysis results for Compound

H NMR results for Compound 2b are given in the following pages .

• Synthesis and analysis results for Compound 2c (N-(4- bromophenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.41 mmol (0.12 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.41 mmol (0.1 gram) of N-(4- bromophenyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2c. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2c at the end of the synthesis is 54%.

Melting point of Compound 2c is about 230-232°C. Compound 2c is yellow.

Compound 2c is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) . However, it is insoluble in distilled water.

Molecular weight of Compound 2c is 534.67 g/mol.

Molecular formula of Compound 2c is C22H2iBrN403S2, and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 25: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2c.

FT-IR analysis results for Compound 2c are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

s . s . b . ( s . b . )

3351, 1330, 1587 1487, 1508 1245 3257, 3186 1163

Table 26: FT-IR analysis results for Compound 2c

H NMR results for Compound 2c are given in the following pages .

• Synthesis and analysis results for Compound 2d (N-(4- chlorophenyl) -2-{l-[4-(4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.5 mmol (0.15 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.5 mmol (0.1 gram) of N-(4- chlorophenyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2d. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2d at the end of the synthesis is 43%.

Melting point of Compound 2d is about 227-228°C. Compound 2d is white.

Compound 2d is soluble in acetone, heated methanol, and dimethyl sulphoxide (DMSO) . However, it is insoluble in chloroform, ethyl acetate, and distilled water.

Molecular weight of Compound 2d is 488.98 g/mol. Molecular formula of Compound 2d is C22H21C IN4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 27: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2d. FT-IR analysis results for Compound 2d are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 28: FT-IR analysis results for Compound 2d.

H NMR results for Compound 2d are given in the following pages . • Synthesis and analysis results for Compound 2e (N-(4- methoxyphenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.52 mmol (0.16 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.52 mmol (0.1 gram) of N-(4- methoxyphenyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis .

Obtaining efficiency of Compound 2e at the end of the synthesis is 37%.

Melting point of Compound 2e is about 190-191°C. Compound 2e is light pink.

Compound 2e is soluble in acetone, chloroform, and dimethyl sulphoxide (DMSO) . However, it is insoluble in methanol, ethyl acetate, and distilled water.

Molecular weight of Compound 2e is 484.57 g/mol.

Molecular formula of Compound 2e is C23H24N4O4 S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

13.23 13.57

Table 29: Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2e.

FT-IR analysis results for Compound 2e are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 30 : FT-IR analysis results for Compound results for Compound 2e are given in the following

• Synthesis and analysis results for Compound 2f (N-(4- methylthiophenyl) -2-{l-[4-(4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.47 mmol (0.14 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.47 mmol (0.1 gram) of N-[4- (methylsulphanyl ) phenyl ] hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2f. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2f at the end of the synthesis is 44%.

Melting point of Compound 2f is about 206-207°C. Compound 2f is brown.

Compound 2f is soluble in acetone, methanol, ethyl acetate, chloroform, and dimethyl sulphoxide (DMSO) . However, it is insoluble in distilled water.

Molecular weight of Compound 2f is 501.54 g/mol.

Molecular formula of Compound 2f is C24H26 4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 31 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2f.

FT-IR analysis results for Compound 2f are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 32 : FT-IR analysis results for Compound

H NMR results for Compound 2f are given in the following pages .

• Synthesis and analysis results for Compound 2g (N- (benzyl) -2-{l- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.55 mmol (0.17 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.55 mmol (0.1 gram) of N- benzylhydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2g at the end of the synthesis is 52%.

Melting point of Compound 2g is about 238-239°C. Compound 2g is light yellow.

Compound 2g is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) . However, it is insoluble in distilled water.

Molecular weight of Compound 2g is 467.57 g/mol.

Molecular formula of Compound 2g is C23H24N4O3S2 , and the theoretically calculated ingredient percentages and the elemental analysis results are as follows.

Table 33 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2g.

FT-IR analysis results for Compound 2g are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

s . s . b . ( s . b . )

3344, 3221 1331, 1593 1491, 1524 1216

1152

Table 3 : FT-IR analysis results for Compound

H NMR results for Compound 2g are given in the following pages .

• Synthesis and analysis results for Compound 2h (N- (2- phenylethyl) -2-{l- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) :

0.52 mmol (0.16 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide is dissolved in 15 mL of methanol and then added onto 0.52 mmol (0.1 gram) of N- (2- phenylethyl ) hydrazinecarbothioamide dissolved in 5 mL of heated methanol as in the method disclosed in the third synthesis. The solid substance obtained in the reaction is Compound 2h. This solid substance is crystallized by filtering and washing with ether.

Obtaining efficiency of Compound 2h at the end of the synthesis is 42%.

Melting point of Compound 2h is about 191-192°C. Compound 2h is white.

Compound 2h is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) . However, it is insoluble in distilled water.

Molecular weight of Compound 2h is 482.61 g/mol. Molecular formula of Compound 2h is C24H26N4O3S2

theoretically calculated ingredient percentages

elemental analysis results are as follows.

Table 35 : Theoretically calculated ingredient percentages and ingredient percentages determined as a result of elemental analysis of Compound 2h. FT-IR analysis results for Compound 2h are given below in terms of wave number (cnf¹) . The meanings of the abbreviations used in the below given table are as follows: s.b. (Stretching band)

s.s.b. (Symmetric stretching band)

as. s.b. (Asymmetric stretching band)

b.b. (Bending band)

Table 36: FT-IR analysis results for Compound 2h.

H NMR results for Compound 2h are given in the following pages . The mechanism of the reaction between the 4-acetylbenzene sulphonylchloride compound that is selected as the starting material of the first synthesis and the aniline derivatives are shown in Figures 21 and 22. Compound 1 or Compound 2 is synthesized according to the hydrogen or methoxy group found in the para position of the aniline derivative used here. In the mechanisms of Figure 21 and 22, one of the n electrons of the S=0 double bond shifts onto one of the oxygen atoms as a result of the attack of the non-pooled electrons of the nitrogen (N) atom found in aniline to the sulphur (S) atom having electrophilic characteristic. As a result of the shift of n electrons to form n bond, chlorine (CI) atom is separated from the structure and one of the hydrogen (H) atoms found on the nitrogen (N) is separated and thus the product is formed.

In the second synthesis, p-substitutedphenyl thiosemicarbazide derivatives are obtained as a result of the interaction of p-substitutedphenyl isothiocyanade derivatives with hydrazine monohydrate in diethylether . When the reaction mechanism shown in Figure 23 is analyzed, it can be seen that, when the hydrazine (:NH₂NH₂) nucleophile attacks the carbon (C) atom found in the isothiocyanade, n electrons are opened on the nitrogen (N) atom, which is more electronegative than the sulphur (S) atom. Thiosemicarbazide derivatives are obtained with the re-arrangement of the molecule due to a shift of a proton found within the molecule .

In the third synthesis, 4-acetyl-N-

( substituted) benzenesulphonamide derivatives are reacted with p-substitutedphenyl thiosemicarbazide to obtain p- substitutedphenyl thiosemicarbazone derivatives. When the reaction mechanism shown in Figure 24 is analyzed, it can be seen that, the nitrogen (N) atom found at the amino end of the thiosemicarbazide attacks the carbonyl carbon (C) of the nitrogen (N) atom. This is because the nitrogen (N) atom found at the amino end has more nucleophilic characteristic than the nitrogen (N) atom of the thioamide group. Following nucleophilic attack, carbonylamine is formed as an unstable intermediate product in the reaction medium. P- substitutedphenyl thiosemicarbazone derivatives are obtained with the re-arrangement of this structure due to the proton transfer within the structure and release of water. HC1 is used in order to provide an acidic medium during the synthesis of p-substitutedphenyl thiosemicarbazone derivatives and the reaction efficiencies are observed to vary between 24-96%.

¹H NMR spectra of the synthesized compounds are shown below. These spectra are taken in a spectrometer device at 400 MHz frequency and the solution is prepared by dissolving about 10 mg of compound in DMSO-d6 for analysis purposes and the prepared solution is analyzed. The chemical shift values of the peaks are evaluated as ppm (parts per million) concentration and the interaction coefficients are given as Hz .

Table 37 : H MR results for synthesized compounds [la-c] .

Table 38 : H NMR results for synthesized compounds [ld-h] .

Table 40: H NMR results for synthesized compounds [2d-h] .

C NMR spectra of the synthesized compounds are taken from a solution of 20 milligrams (mg) of substance in CDCI₃ and DMSO-d6, in a spectrometer device at 400 MHz frequency. In said spectra, tetramethylsilane (TMS) is accepted as standard. The chemical shift values of the determined peaks are evaluated as ppm (parts per million) concentration and the interaction coefficients are given as Hz. ¹³C NMR results for Compound lc, lh, 2a, and 2h in the thiosemicarbazone derivatives synthesized according to the method of the invention are given below.

Table 41: C NMR results for synthesized compounds [lc, lh, 2a,

2h]

Thin-layer chromatography (TLC) is used for monitoring the process of reactions during the synthesis works and determining the purity levels of obtained compounds. For this purpose, 20x20 cm chromatographic plates coated with 0-25 millimetre (mm) thickness of silica gel are used as adsorbent. Ethyl acetate and n-hexane (3:2, 3:1, 1:1) are used as solvent system. The operation of sweeping the solvent on the plates is performed after solvent systems are placed in chromatography tanks at room temperature and the tanks are saturated with solvent vapour. After the sweeping operation is complete, in order to make the stains found on the air-dried plates visible, the plates are required to be observed under UV light at 254 nanometres (nm) wavelength. In order to obtain a clearer view, the plates should be placed in a closed tank saturated with iodine vapour. In the third synthesis, which is the synthesis of thiosemicarbazide derivatives, while the reaction is being monitored, dimethylamino benzaldehyde (DAB) reagent is sprayed into the reaction medium and the presence of hydrazine hydrate residue is determined in the medium.

FT-IR (Fourier Transform-Infrared) spectra is obtained in the wave number of 4000-400 cnf¹ and via direct solid sample. FT-IR analysis results of synthesized compounds are shown in the below given Tables 42 and 43.

Theoretically calculated ingredient percentages and elemental analysis (CHNS) results of synthesized compounds are given below in Tables 44 and 45.

Below given Tables 46 and 47 show the closed formulas, molecular weights, melting points, and obtaining efficiencies of synthesized compounds.

Table 42: FT-IR results of synthesized compounds [la-h]

Table 43: FT-IR results of synthesized compounds [2a-h] .

Table 44: Closed formulas, theoretically calculated ingredient percentages, and elemental analysis (CHNS determination) results of synthesized compounds [ 1 , la-h] .

Table 45: Closed formulas, theoretically calculated ingredient percentages, and elemental analysis (CHNS determination) results of synthesized compounds [2, 2a-h] .

Table 46: Closed formulas, molecular weights, melting points, and obtaining efficiencies synthesized compounds [1, 2, la-g] .

Table 47: Closed formulas, molecular weights, melting points, and obtaining efficiencies synthesized compounds [lh, 2a-h] .

Description of the Figures

Figure 1: Chemical structure of Compound 1 (4-acetyl-N- phenylbenzenesulphonamide ) that is the product of the first synthesis .

Figure 2: Chemical structure of Compound 2 (4-acetyl-N-

(methoxyphenyl ) benzenesulphonamide ) that is the product of the second synthesis.

Figure 3: Chemical structure of Compound la (N-cyclohexyl-2-

{ 1- [ 4 -phenyl sulphamoylphenyl ] ethylidene } hydrazine

carbothioamide ) that is the product of the third synthesis.

Figure 4: Chemical structure of Compound lb (N-phenyl-2- { 1-

[ 4 -phenyl sulphamoylphenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 5: Chemical structure of Compound lc (N-(4- bromophenyl ) -2- { 1- [ 4-

(phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 6: Chemical structure of Compound Id (N-(4- chlorophenyl ) -2- { 1- [ 4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 7: Chemical structure of Compound le (N-(4- methoxyphenyl ) -2- { 1-

(phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 8: Chemical structure of Compound If (N-(4- methylthiophenyl ) -2- { 1- [ 4-

(phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis. Figure 9: Chemical structure of Compound lg (N- (benzyl ) -2-

{1- [4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis. Figure 10: Chemical structure of Compound lh (N- (2- phenylethyl) -2-{l- [4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide ) that is the product of the third synthesis. Figure 11: Chemical structure of Compound 2a (N- (cyclohexyl) -2-{l- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis. Figure 12: Chemical structure of Compound 2b (N- (phenyl ) -2- {1- [4- (4-methoxyphenylsulphamoyl ] phenyl ] ethylidene } hydrazine carbothioamide) that is the product of the third synthesis. Figure 13: Chemical structure of Compound 2c (N-(4- bromophenyl ) -2- { 1- [4- (4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 14: Chemical structure of Compound 2d (N-(4- chlorophenyl) -2- { 1- [4- (4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 15: Chemical structure of Compound 2e (N-(4- methoxyphenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 16: Chemical structure of Compound 2f (N-(4- methylthiophenyl) -2-{l-[4-(4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis.

Figure 17: Chemical structure of Compound 2g (N- (benzyl ) -2- {1- [4- (4-methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide) that is the product of the third synthesis. Figure 18: Chemical structure of Compound 2h (N- (2- phenylethyl) -2- { 1- [4- (4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) that is the product of the third synthesis. Figure 19: Chemical structure showing the protons of Compound la (N-cyclohexyl-2- { 1- [ 4- phenylsulphamoylphenyl ] ethylidene } hydrazine carbothioamide ) , Compound lb (N-phenyl-2- { 1- [ 4- phenylsulphamoylphenyl ] ethylidene } hydrazine carbothioamide) , Compound lc (N- ( 4-bromophenyl ) -2- { 1- [ 4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound Id (N- ( chlorophenyl ) -2- { 1- [ 4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound le (N- ( 4-methoxyphenyl ) -2- { 1- [ 4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound If (N- ( 4-methylthiophenyl ) -2- { 1-

[4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound lg (N- (benzyl ) -2- { 1- [ 4-

(phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), and Compound lh (N- (2-phenylethyl ) -2- { 1- [ 4- (phenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide) when Compound 1 (4-acetyl-N- phenylbenzenesulphonamide ) is used as the starting material in the third synthesis.

Figure 20: Chemical structure showing the protons of Compound 2a (N- (cyclohexyl) -2- { 1- [4- (4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound 2b (N- (phenyl ) -2- { 1- [ 4- ( 4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound 2c (N- ( 4-bromophenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound 2d (N- ( 4-chlorophenyl ) -2- { 1- [ 4- ( 4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), Compound 2e (N- ( 4-methoxyphenyl ) -2- { 1- [ 4- ( 4-methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ), Compound 2f (N- ( 4-methylthiophenyl ) -2- { 1- [ 4-

( 4-methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide), Compound 2g (N- (benzyl ) -2- { 1- [ 4- ( 4- methoxyphenyl sulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide), and Compound 2h (N- (2-phenylethyl) -2- { 1- [4- ( 4-methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide ) when Compound 2 ( 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide ) is used as the starting material in the third synthesis.

Figure 21: The mechanism for obtaining Compound 1 (4-acetyl- N-phenylbenzenesulphonamide ) that is the sulphonamide derivative product of the first synthesis.

Figure 22: The mechanism for obtaining Compound 2 (4-acetyl- N- ( 4-methoxyphenyl ) benzenesulphonamide ) that is the sulphonamide derivative product of the first synthesis.

Figure 23: The mechanism for obtaining the second synthesis product thiosemicarbazide derivatives.

Figure 24: The mechanism for obtaining the third synthesis product thiosemicarbazone derivatives.

Claims

1. A synthesis method of thiosemicarbazone derivatives, characterized in that; it comprises the process steps of:

- in the first synthesis; reacting 4-acetylbenzene sulphonylchloride with aniline or p-methoxyaniline, at room temperature, in the presence of dichloromethane,

- as a result of this reaction; formation of Compound 1 (4- acetyl-N-phenylbenzenesulphonamide ) , which is a sulphonamide derivative, or Compound 2 ( 4-acetyl-N- ( 4-methoxyphenyl ) benzene sulphonamide) ;

in the second synthesis; reacting 4-substitutedphenyl isothiocyanade derivatives with hydrazine monohydrate, in the presence of diethylether, at room temperature;

- as a result of this reaction; formation of thiosemicarbazide derivatives ;

- in the third synthesis; reacting a sulphonamide derivative obtained in the first synthesis with a thiosemicarbazide derivative obtained in the second synthesis, in the presence of methyl alcohol, by heating;

- as a result of this reaction; formation of thiosemicarbazone derivatives .

2 . The synthesis method of thiosemicarbazone derivatives according to Claim 1, characterized in that; in the first synthesis, it comprises the process steps of:

- dissolving 1.17 mmol of aniline or p-methoxyaniline in 10 ml of dichloromethane;

adding 1.06 mmol triethylamine and 1-3 drops of pyridine onto this mixture as catalysts;

- mixing this mixture at room temperature for 15 minutes;

- in a separated part, dissolving 1.06 mmol of 4- acetylbenzenesulphonyl chloride in 5 mL of dichloromethane and adding onto the above prepared mixture; - heating the mixture during and/or following this addition;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- applying extraction operation on the cooled mixture via 2 M hydrochloric acid (HC1);

drying organic phases with sodium sulphate following extraction operation;

washing the crystals formed as a result of the drying operation with petroleum ether; and

- obtaining 4-acetyl-N-phenylbenzenesulphonamide or 4-acetyl- N- ( 4-methoxyphenyl ) benzenesulphonamide following washing operation .

3 . The synthesis method of thiosemicarbazone derivatives according to Claim 1, characterized in that; in the second synthesis, it comprises the process steps of:

dissolving 1 mmol 4-substitutedphenyl isothiocyanade derivative in diethylether;

- adding 1 mmol hydrazine monohydrate dissolved in diethylether into this mixture;

- formation of solid substances at the bottom of the mixture following the addition;

- taking these solid substances from the mixture vessel;

- crystallization of these solid substances in a solvent; and obtaining thiosemicarbazide derivatives following crystallization operation.

4 . The synthesis method of thiosemicarbazone derivatives according to Claim 1, characterized in that; in the third synthesis, it comprises the process steps of:

- dissolving thiosemicarbazide derivative in heated methanol; - adding sulphonamide derivative, which has the same number of moles with the thiosemicarbazide derivative that was added first, dissolved in methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances in a solvent; and obtaining thiosemicarbazone derivatives following crystallization operation.

5 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.58 mmol (0.1 gram) of N- cyclohexylhydrazinecarbothioamide in 5 mL of heated methanol; - adding 0.58 mmol (0.16 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N-cyclohexyl-2- { 1- [ 4-phenylsulphamoylphenyl ] ethylidene } hydrazine following crystallization operation.

6. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.59 mmol (0.1 gram) of N- phenylhydrazinecarbothioamide in 5 mL of heated methanol;

adding 0.59 mmol (0.17 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N-phenyl-2- { 1- [ 4- (phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide following crystallization operation.

7 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

- dissolving 0.41 mmol (0.1 gram) of N-(4- bromophenyl ) hydrazinecarbothioamide in 5 mL of heated methanol ;

adding 0.41 mmol (0.11 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature; - formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 4-bromophenyl ) -2- { 1- [ 4- (phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide following crystallization process.

8 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.50 mmol (0.1 gram) of N-(4- chlorophenyl ) hydrazine carbothioamide in 5 mL of heated methanol;

adding 0.50 mmol (0.14 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 4-chlorophenyl ) -2- { 1- [ 4- (phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide following crystallization process.

9. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of: dissolving 0.52 mmol (0.1 gram) of N-(4- methoxyphenyl ) hydrazine carbothioamide in 5 mL of heated methanol ;

adding 0.52 mmol (0.14 grams) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 4-methoxyphenyl ) hydrazinecarbothioamide following crystallization operation.

10 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.47 mmol (0.1 gram) of N-[4-

(methylsulphanyl ) phenyl ] hydrazinecarbothioamide in 5 mL of heated methanol;

- adding 0.47 mmol (0.13 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture; - crystallization of these solid substances by washing with ether;

obtaining N- ( 4-methylthiophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide following crystallization process.

11. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

- dissolving 0.55 mmol (0.1 gram) of N- benzylhydrazinecarbothioamide in 5 mL of heated methanol;

adding 0.55 mmol (0.15 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL of methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- (benzyl ) -2- { 1- [ 4- (phenylsulphamoyl ) phenyl ] ethylidene} hydrazine carbothioamide following crystallization process .

12. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.51 mmol (0.1 gram) of N- (2- phenylethyl ) hydrazine carbothioamide in 5 mL of heated methanol ; adding 0.51 mmol (0.14 gram) of 4-acetyl-N- phenylbenzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 2-phenylethyl ) -2- { 1- [ 4- (phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide following crystallization process.

13. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

- dissolving 0.58 mmol (0.1 gram) of N- cyclohexylhydrazinecarbothioamide in 5 mL of heated methanol; adding 0.58 mmol (0.17 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether; obtaining N- (cyclohexyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

14 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.6 mmol (0.1 gram) of N- phenylhydrazinecarbothioamide in 5 mL of heated methanol;

- adding 0.6 mmol (0.18 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- (phenyl) -2- { 1- [4- (4-methoxyphenylsulphamoyl) phenyl ] ethylidene } hydrazine carbothioamide following crystallization process.

15 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.41 mmol (0.1 gram) of N-(4- bromophenyl ) hydrazinecarbothioamide in 5 mL of heated methanol ;

adding 0.41 mmol (0.12 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture; - heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

- obtaining N- ( 4-bromophenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

16 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.5 mmol (0.1 gram) of N-(4- chlorophenyl ) hydrazinecarbothioamide in 5 mL of heated methanol ;

- adding 0.5 mmol (0.15 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 4-chlorophenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

17. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

- dissolving 0.52 mmol (0.1 gram) of N-(4- methoxyphenyl ) hydrazinecarbothioamide in 5 mL of heated methanol ;

adding 0.52 mmol (0.16 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

- obtaining N- ( 4-methoxyphenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

18. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.47 mmol (0.1 gram) of N-[4-

(methylsulphanyl ) phenyl ] hydrazinecarbothioamide in 5 mL of heated methanol;

- adding 0.47 mmol (0.14 gram) of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours; - completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 4-methylthiophenyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

19 . The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.55 mmol (0.1 gram) of N- benzylhydrazinecarbothioamide in 5 mL of heated methanol;

adding 0.55 mmol (0.17 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

- obtaining N- (benzyl) -2- { 1- [4- ( 4-methoxyphenylsulphamoyl ) phenyl] ethylidene } hydrazinecarbothioamide following crystallization operation.

20. The synthesis method of thiosemicarbazone derivatives according to Claim 4, characterized in that; it comprises the process steps of:

dissolving 0.52 mmol (0.1 gram) of N- (2- phenylethyl ) hydrazinecarbothioamide in 5 mL of heated methanol ;

adding 0.52 mmol (0.16 gram) of 4-acetyl-N- (4- methoxyphenyl ) benzenesulphonamide dissolved in 15 mL methanol onto this mixture;

- heating this reaction mixture for 48 hours;

- completion of the reaction when the starting material of the mixture is used up, and then cooling of the mixture to the room temperature;

- formation of solid substances at the bottom of the mixture following the cooling operation;

- removing the formed solid substances from the mixture;

- crystallization of these solid substances by washing with ether;

obtaining N- ( 2-phenylethyl ) -2- { 1- [4- (4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazine

carbothioamide following crystallization process.

21. Sulphonamide derivatives obtained with a method according to Claim 2.

22. Sulphonamide derivatives according to Claim 21, characterized in comprising:

- the compound of 4-acetyl-N-phenylbenzenesulphonamide, which has a molecular formula of C₁₄H₁₃NO₃S and molecular weight of 275.32 g/mol which

- has a melting point of 83-84°C,

- has dust form and orange colour,

- is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, and - is insoluble in distilled water.

23 . Sulphonamide derivatives according to Claim 21, characterized in comprising:

the compound of 4-acetyl-N- ( 4- methoxyphenyl ) benzenesulphonamide, which has a molecular formula of C₁₅H₁₅NO₄S and molecular weight of 305.84 g/mol which

- has a melting point of 114-115°C,

- has dust form and brown colour,

- is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, and

- is insoluble in distilled water.

24 . Thiosemicarbazide derivatives obtained with a method according to Claim 3.

25 . Thiosemicarbazone derivatives obtained with a method according to any one of Claims 4 to 20.

26 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N-cyclohexyl-2- { 1- [ 4- phenylsulphamoylphenyl ] ethylidene } hydrazine, which has a molecular formula of C21H2₆ 4O2 S2 and molecular weight of 430.59 g/mol which

- has a melting point of 228-230°C,

- has yellow colour,

- is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , heated chloroform, and heated methyl acetate, and

- is insoluble in distilled water.

27. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N-phenyl-2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazine carbothioamide, which has a molecular formula of C21H2₀ 4O2 S2 and molecular weight of 424.54 g/mol which

- has a melting point of 182-184°C,

- has yellow colour,

- is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , and chloroform, and

- is insoluble in distilled water and ethyl acetate.

28. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

- the compound of N- ( 4-bromophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinekarbothioamide, which has a molecular formula of C₂iHi₉BrN₄0₂S₂ and molecular weight of 503.44 g/mol which

- has a melting point of 212-214°C,

- has yellow colour,

is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) ,

is insoluble in chloroform, ethyl acetate, and distilled water .

29. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 4-chlorophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide, which has a molecular formula of C21H1₉C IN4O2 S2 and molecular weight of 458.98 g/mol which

- has a melting point of 213-215°C,

- has yellow colour, is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) ,

is insoluble in chloroform, ethyl acetate, and distilled water .

30. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 4-methoxyphenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide, which has a molecular formula of C22H22 4O3S2 and molecular weight of 454.57 g/mol which

- has a melting point of 195-197°C,

- has light pink colour,

- is soluble in acetone, methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, and

- is insoluble in distilled water.

31. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

- the compound of N- ( 4-methylthiophenyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide, which has a molecular formula of C22H22 4O2 S 3 and molecular weight of 470.54 g/mol which

- has a melting point of 176-178°C,

- has yellow colour,

- is soluble in acetone, heated methanol, dimethyl sulphoxide (DMSO) , chloroform, and ethyl acetate, and

- is insoluble in distilled water.

32. Thiosemicarbazone derivatives according to Claim 25 characterized in comprising:

the compound of N- (benzyl ) -2- { 1- [ 4

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide, which has a molecular formula of C22H22N4O2 S2 and molecular weight of 438.57 g/mol which

- has a melting point of 183-185°C,

- has yellow colour,

- is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) ,

is insoluble in chloroform, ethyl acetate, and distilled water .

33 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 2-phenylethyl ) -2- { 1- [ 4-

(phenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioamide, which has a molecular formula of C23H24N4O2 S2 and molecular weight of 452.57 g/mol which

- has a melting point of 195-197°C,

- has yellow colour,

is soluble in acetone, methanol, and dimethyl sulphoxide (DMSO) ,

- is insoluble in chloroform, ethyl acetate, and distilled water .

34 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

- the compound of N- (cyclohexyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C22H28 4O3S2 and molecular weight of 460.59 g/mol which

- has a melting point of 220-221°C,

- has yellow colour,

is soluble in acetone, heated methanol, chloroform, and dimethyl sulphoxide (DMSO) ,

- is insoluble in ethyl acetate and distilled water.

35 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- (phenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C22H21 4O₃S2 and molecular weight of 454.81 g/mol which

- has a melting point of 190-191°C,

- has white colour,

- is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) ,

- is insoluble in distilled water.

36 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

- the compound of N- ( 4-bromophenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C₂₂H₂iBrN₄0₃S2 and molecular weight of 534.67 g/mol which

- has a melting point of 230-232°C,

- has yellow colour,

- is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) ,

- is insoluble in distilled water.

37 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 4-chlorophenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C22H21C IN4O₃S2 and molecular weight of 488.98 g/mol which

- has a melting point of 227-228°C,

- has white colour,

is soluble in acetone, heated methanol, and dimethyl sulphoxide (DMSO) , is insoluble in chloroform, ethyl acetate, and distilled water .

38 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 4-methoxyphenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C23H24N4O4 S2 and molecular weight of 484.57 g/mol which

- has a melting point of 190-191°C,

- has light pink colour,

- is soluble in acetone, chloroform, and dimethyl sulphoxide (DMSO) ,

is insoluble in methanol, ethyl acetate, and distilled water.

39 . Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 4-methylthiophenyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C24H26 4O3S2 and molecular weight of 501.54 g/mol which

- has a melting point of 206-207°C,

- is brown,

- is soluble in acetone, methanol, ethyl acetate, chloroform, and dimethyl sulphoxide (DMSO) ,

- is insoluble in distilled water.

40. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- (benzyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C23H24N4O3S2 and molecular weight of 467.57 g/mol which - has a melting point of 238-239°C,

- has yellow colour,

- is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) ,

- is insoluble in distilled water.

41. Thiosemicarbazone derivatives according to Claim 25, characterized in comprising:

the compound of N- ( 2-phenylethyl ) -2- { 1- [ 4- ( 4- methoxyphenylsulphamoyl ) phenyl ] ethylidene } hydrazinecarbothioam ide, which has a molecular formula of C24H26 4O3S2 and molecular weight of 482.61 g/mol which

- has a melting point of 191-192°C,

- has white colour,

- is soluble in acetone, methanol, chloroform, ethyl acetate, and dimethyl sulphoxide (DMSO) ,

- is insoluble in distilled water.