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Document Type : Original Article

Authors

1 Ministry of Education General Directorate of Baghdad Governorate, Rusafa/3, Iraq

2 Department of Chemistry, College of Education for Pure Science (Ibn al-Haitham), University of Baghdad, Iraq

Abstract

In this study, some azomethine compounds were prepared from 4-hydroxybenzoic acid hydrazide with some primary amine derivatives in different ways from the usual methods. The method used in research is utilizing water as solvent instead of any other organic solvent. In addition, lab-made microwave was used instead of hot plate or reflux method. P-hydroxy ethyl benzoate was treated directly with hydrazine hydrate in microwave oven which gave hydrazide derivative in a very short time; hydrazide derivative (1) was reacted with some carbonyl compounds (aldehyde derivatives) to produce of some Schiff base derivatives (compounds 2-14). None of these azomethine derivatives exceeded 10 minutes in lab-made micro wave and using water as solvent. Compounds (2-14) were treated with acetic anhydride in microwave oven to synthesized of some 1,3,4-oxadiazole derivatives (15-23). All compounds high yield, short time, low cost in comparison with traditionally methods. The prepared compounds were characterized by melting points, 1H-NMR, and FT-IR.

Graphical Abstract

Eco-friendly, Rapid Synthesis of Some 4-Hydroxybenzoic Acid Hydrazide Derivatives

Keywords

Main Subjects

Introduction

Microwave irradiation method is a better than heating method (reflux) and it is also a better method than the ones using organic solvents such as ethanol, methanol, dimethyl formamide, chloroform, acetone, benzene, and dimethylsulfoxide [1].

Traditional methods may cause damages to the health of humans, animals, and the surrounding environment because of the all classical reactions producing fumes that are harmful to health and environment [2]. Green chemistry is one of the most important sciences in environmental field [3]. It can be defined as a branch of science which utilizes a set of principles for the invention, design, development, and implementation of chemical processes that reduce or eliminate the use and generation of hazardous substances [4]. There are many advantages in a chemical synthesis in green chemistry such as high yield, rapid synthesis, reduce the damage of the environmental, declines waste to even waste disposal in the correct way, all chemical wastes should be better disposed without causing any damage to the environment and organisms [5].

Recently, new methods have been used to prepare some organic compounds such as microwave synthesis for preparing some chemical compounds, Schiff bases, some heterocyclic rings, macro cycle compounds, and some inorganic compounds (complexes). Some researchers were synthesis of some pyrazole, pyridine derivatives under microwave irradiation [6, 7] were synthesized by some derivative of N-benzylidene-6-methoxybenzo[d]thiazol-2-amine under microwave method. Some researchers prepared some azomethine derivatives containing fluoro atom under microwave irradiation [8].

Oxadiazole derivatives are important in heterocyclic compounds and their importance is due to their applications in pharmaceutical fields [9, 10]. The well-known methods of preparing oxadiazole derivatives are classic methods, but in this research, the irradiation of microwave was utilized for preparing N-acetyl 1,3,4-oxadiazole derivatives.

Materials and Methods

Preparation of p-hydroxybenzohydrazide [11]

A mixture of ethyl 4-hydroxybenzoate (0.1 mol, 0.166 g) with hydrazine hydrate in (25 mL) of ethanol all mixture compounds were reflux under (60-70 °C) for 2 hours, the precipitate was filtered and recrystallized from methanol (yield 65%, m.p=263 (°C lit m.p=262 °C) (Scheme 1).

Scheme 1: Preparation of p-hydroxybenzohydrazide

Preparation of 4-hydroxybenzohydrazide under lab-made microwave irradiation

2 mL of hydrazine hydrate with 0.166 g of ethyl p-hydroxybenzoate were placed in a conical flask, and then it was transferred to a lab-made microwave at 180 watts for 3 minutes the product was filtered and collected the precipitate without recrystallization, (yield 93%, m.p=265 °C) (Scheme 2).

 

Scheme 2: Preparation 4-hydroxybenzohydrazide under microwave irradiation

Preparation of some Schiff base of N'-substituted-4-hydroxybenzohydrazide (2-14) [12, 13]

Some derivatives of aromatic aldehyde (0.01 mol) with a 4-hydroxybenzohydrazide were refluxed for 3-7 hours in 50 mL of ethanol the mixture (Scheme 3). The reaction was monitored by thin layer chromatography to determine the end time of the reaction. Then, the product was filtered and washed with cold methanol and recrystallized from a suitable solvent (Table 1).

 

Scheme 3: Synthesis of Schiff bases

Table 1: Nomenclature and physical properties of all synthesized compounds

Preparation of some Schiff base of N'-substituted-4-hydroxybenzohydrazide under lab-made microwave (2-14) [14]

A mixture of hydrazide with some aromatic aldehyde were placed in a container with (3 mL) of ethanol the reaction mixture was placed in a lab-made microwave (180-360) watts at 3-8 minutes according to the type of aromatic aldehyde (Scheme 4). Then, the product was washed with cold water, filtered, and collected (Table 1).

Scheme 4: Synthesis of Schiff base under microwave irradiation

Synthesis of 1-(5-(4-hydroxyphenyl)-2-Aryl-1,3,4-oxadiazol-3(2H)-yl)ethenone (15-23)

Acetic anhydride (50 mL) as solvent and reactant was reacted with some Schiff bases (2-10) in a round flask (150 mL) the mixture reaction was refluxed for 5-17 hours, with monitored the reaction by thin layer chromatography (Scheme 5). The precipitate was filtered and recrystallized from a suitable solvent, all physical properties and yields can be reviewed in Table 1.

Synthesis of 1-(5-(4-hydroxyphenyl)-2-Aryl-1,3,4-oxadiazol-3(2H)-yl)ethanone(15-23) under lab-made microwave

Under irradiation of lab-made microwave, the mixture reaction of Schiff base with 5 mL of acetic anhydride in a beaked 25 mL moved to oven and shed radiation for this reaction (10-40) minutes. The reaction mixture was allowed to be cooled and poured onto the ice water, after filtration has been recrystallized from a suitable solvent (Scheme 6). The calculation of yield and melting point are listed in Table 1.

Scheme 5: Synthesis of 1-(5-(4-hydroxyphenyl)-2-Aryl-1,3,4-oxadiazol-3(2H)-yl)ethenone

Scheme 6: Synthesis of 1-(5-(4-hydroxyphenyl)-2-Aryl-1,3,4-oxadiazol-3(2H)-yl)ethanone under microwave irradiation

Results and Discussion

In this research, two methods were used for preparing some derivatives of substituted of p-hydroxy benzoic acid hydrazide, all prepared compounds have been characterized by using melting points, Fourier transform infrared, and 1H-NMR.

Acid hydrazide of hydroxy benzoic acid was prepared under reflux and microwave irradiation. Through these two methods, it was concluded that the microwave method is better than the usual method because it has the advantage of having a shorter time, higher yield, low cost, and less amount of solvent. Infrared spectroscopy results for compound 1 showed new band at 1649 cm-1 due to of carbonyl of hydrazide, which was added to that appeared a new band at 3217 and 3321 cm-1 for amine of hydrazide.

A series of compounds (2-14) were prepared from the reaction of acid hydrazide (1) with some derivatives of aromatic aldehyde under room temperature, reflux, and microwave irradiation. It was noted that all of these methods gave similar characterized results, but the difference in time, yield, and solvent. Reflux method revealed prepared compounds with longer time reaction and low yield with comparison with microwave irradiation. Preparation of compounds (2-14) under microwave irradiation revealed good results as it proved to be the best method than the usual one especially time, yield, cost, and solvent, all derivative compounds (2-14) prepared under lab-made microwave at (4-8) minutes with yield between 90-97% without recrystallization and water as solvent, but the time reaction of reflux method with 2-5 hours, yielded (60-75%) with recrystallized from a suitable solvents. The results of infrared spectroscopy showed a new band at 1590-1615 cm-1 due to of imine groups and disappearance band at 3217 and 3321 cm-1 of primary amine, all data of these compounds is depicted in Table 2, 1H-NMR of compounds (2-14) showed peak at 9.92-1.11 ppm for hydroxyl group in phenol and a singlet signal at 8.50-8.70 ppm for CH=N for azomethine group, signal at 11.31-11.94 ppm for NH peak. N-acetyl 1,3,4-oxadiazole derivatives can be prepared from Schiff bases of acid hydrazide with acetic anhydride this reaction is known and characterized by a long reaction time, but in this research, microwave method was used for preparing N-acetyl 1,3,4-oxadiazole derivatives (15-23) (Table 3).

This method has several advantages. It can be counted with some points, short-time reaction, lower energy consumption, high yield, and high purity for the product. The FT-IR spectroscopy showed a good evidence for prepared of oxadiazole ring, all spectrums of infrared spectroscopy showed a new band at 1704-1755 cm-1 for C=O amide, disappeared of azomethine and NH bands at 3230-3383 cm-1, respectively. 1H-NMR of compounds 15-23 reveals disappearance peaks of CH=N and NH at 8.50-8.70, 11.31-11.94 ppm, respectively and new peak at 2.19-2.41 ppm for methyl group. All data for proton NMR of compounds 15-23 are listed in Table 4 and 5.

 

Table 2: FT-IR of compounds 2-14

Compounds

OH

C=O

NH

C=N

CH aliph

CH Ar

Others

2

3281

1638

3325

1619

2935

3195

OH (3325)

3

3243

1620

3383

1599

2963

3085

C-O (1219)

4

3150

1655

3338

1604

2931

3081

NO2 (1338, 1549)

5

3195

1609

3315

1590

2909

3139

-

6

3205

1627

3277

1603

2919

3031

-

7

3208

1644

3305

1601

2970

3091

NO2 (1349, 1560)

8

3109

1633

3230

1607

2943

3031

-

9

3137

1634

3250

1620

2943

3084

-

10

3270

1636

3270

1601

2929

3075

OH (3506)

11

3135

1638

3319

1615

2972

3080

OH (3531)

12

3194

1606

3272

1588

2958

3049

OH (33080

13

3185

1642

3358

1603

2906

3055

-

14

3110

1639

3204

1606

2990

3039

-

 

Table 3: FT-IR of compounds 15-23

Component

OH (cm-1)

C=O

(Oxadiazole) (cm-1)

C=N

(Oxadiazole)

(cm-1)

CH aliph

(cm-1)

CH Ar

(cm-1)

Others

(cm-1)

15

3181

1748

1655

2924

3004

OH (3347)

16

3100

1753

1666

2952

3035

NO2 (1353,1521)

17

3113

1752

1656

2936

3064

-

18

3102

1753

1662

2969

3036

-

19

3225

1748

1688

2936

3030

-

20

3220

1749

1628

2939

3038

OH (3319)

21

3266

1757

1625

2947

3030

OH (3293)

22

3166

1755

1629

2942

3079

OH (3257)

23

3109

1704

1630

2921

3047

NO2 (1344,1595)

 

Table 4: 1H-NMR of Schiff base derivatives

Component

N-H (ppm)

OH (ppm)

CH=N

Others

2

11.50

10.10

8.59

OH (9.09 ppm)

4

11.94

10.18

8.50

-

5

11.31

9.92

-

(-CH3), (-CH2) 1.82,4.35

11

11.40

11.11

8.58

(OH) 10.17

14

11.88

9.62

8.70

-

 

Table 5: 1H-NMR of 1,3,4-oxadiazole derivatives

Component

OH (ppm)

-(CH3)

H-aromatic

Others

15

9.85

2.27

m (7.19-7.91)

(-OH) s, 9.67

19

8.99

2.29

m (6.95-7.95)

 (-CH3) s, 2.39

20

9.92

2.19

m (7.43-7.99)

(-OH) s, 9.54

22

9.92

2.25

m (7.17-7.47)

(-OCH3), s 1.88

23

10.15

2.41

m (8.03-8.44)

-

 

Conclusion

All synthesized compounds in this research were prepared by two methods traditional and non-classical methods. The non-classical method means the preparation of compounds under lab-made microwave. The results indicate the advantage of using irradiation microwave by comparing reflux method for the following reasons:

Microwave irradiation is featured, short time, small amount of solvent, high yield, high purity, and eco-friendly. For preparing Schiff bases in this research, water was used as solvent instead of ethanol or methanol, the use of water in this method is a good point because it is cheap, safe for the environment, and short time needed for doing the reaction.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Conflict of Interest

There are no conflicts of interest in this study.

ORCID:

Huda H. Saeed

https://orcid.org/0000-0001-9622-6255

Ismaeel Y. Majeed

https://www.orcid.org/0000-0001-9622-6255

HOW TO CITE THIS ARTICLE

Huda H. Saeed, Ismaeel Y. Majeed. Eco-friendly, Rapid Synthesis of Some 4-Hydroxybenzoic Acid Hydrazide Derivatives. Chem. Methodol., 2022, 6(10) 773-782

https://doi.org/10.22034/CHEMM.2022.350693.1572

URL: http://www.chemmethod.com/article_153728.html

 

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