UDEC3134 GREEN CHEMISTRY

NAME: HARVINDAEN A/L MUNIANDY (1606466)

:CHAI JIAN WEI (1504143)

EXPERIMENT NUMBER: 4

EXPERIMENT TITTLE: SYNTHESIS OF

DIHYDROPYRANOL[2,30C]PYRAZOLE UNDER
ULTRASOUND IRRADIATION

DATE OF EXPERIMENT: 26/02/2019

PRACTICAL GROUP: 2

DATE OF SUBMISSION: 16/03/2019

LECTURER NAME: DR MOHAMMOD AMINUZZAMAN

Tittle: Synthesis of dihydropyranol[2,3-c]pyrazole under ultrasound irradiation.

Objective:

1) To synthesize dihydropyrano[2,3-c]pyrazole in water under ultrasound irradiation.

2) To determine the percentage yield of dihydropyrano[2,3-c]pyrazole.

3) To determine the melting point of dihydropyrano[2,3-c]pyrazole.

Introduction:

In the recent years, being focused on green chemistry using environmentally benign reagents

and conditions is one of the most fascinating developments in synthesis of widely used

organic compounds. The use of water as a promising solvent for organic reactions has

received considerable attention in the arena of organic synthesis owing to its green

credentials, and organic synthesis in aqueous media offering key advantages such as rate

enhancement and insolubility of the final products, which facilitates their isolation by simple

filtration.

Nitrogen-containing heterocyclic compounds are widespread in natural products and

medicinal agents, and their applications to biologically active pharmaceuticals,

agrochemicals, and functional materials are becoming more and more important. Among

them, dihydropyrano[2,3-c]pyrazoles are very interesting compounds and have received

considerable attention as a result of their biological activity and an interesting template for

medicinal chemistry. Many of those compounds are known as antimicrobial, insecticidal, and

anti-inflammatory. Furthermore, dihydropyrano[2,3-c]pyrazoles showed molluscicidal

activity and was identified as a screening hit for Chk1 kinase inhibitor.

Ultrasound technique has increasingly been used in organic synthesis in the recent years. A

large number of organic reactions can be carried out in a higher yield, shorter reaction time
and milder conditions under ultrasonication. Compared with traditional methods, this method

is more convenient and can be easily controlled. In this experiment, the students will carry

out the synthesis of dihydropyrano-[2,3-c]pyrazoles in water under ultrasound irradiation.

Procedures:

Hydrazine (3.0 mmol), ethyl acetoacetate (2.0 mmol), aldehyde (2.0 mmol) and malononitrile

(2 mmol) were mixed in distilled water (15 mL) in a 100 mL round bottomed flask. The

mixture was sonicated in the water bath of an ultrasonic cleaner at 50 °C for 30 minutes.

After the completion of reaction, the reaction was allowed to cool in ice bath. The solid crude

product was filtered by vacuum filtration. The crude product was recrystallized in 5-10 mL of

hot ethanol. Then, the mixture was cooled in ice bath for recrystallization. The crystal was

filtered by vacuum filtration and washed with cold water. The yields of products obtained

were calculated. The melting points of the products were measured and compared with

literature values.

Results and Calculation:

Using 4-chlorobenzaldehyde:

Mass of hydrazine = 0.1722 g

Mass of ethyl acetoacetate = 0.2603 g

Mass of 4-chlorobenzaldehyde = 0.2806 g

Mass of malononitrile = 0.1362 g

Mass of filter paper = 0.6727 g

Mass of filter paper + product = 1.8727 g

Mass of product = 1.2000 g

Melting point of product = 186 – 187 ℃

Based on above equation 1 mole of hydrazine reacts with 1 mole of ethyl acetoacetate, 1

mole of 4-chlorobenzaldehyde and 1 mole of malononitrile to produce 1 mole of

dihydropyrano-[2,3-c]pyrazoles. In the synthesis that has been done 3 mmole of hydrazine

reacts with 2 mmole of ethyl acetoacetate, 2 mmole of 4-chlorobenzaldehyde and 2 mmole of

malononitrile to produce 2 mmole of dihydropyrano-[2,3-c]pyrazoles. Ethyl acetoacetate, 4-

chlorobenzaldehyde and malononitrile are limiting reagents.

Theoretical mass of dihydropyrano-[2,3-c]pyrazoles = No. of mole × Molecular mass

= 2 mmol × 285.71 g/mol
= 0.5714 g

Percentage yield of dihydropyrano-[2,3-c]pyrazoles

= (Actual mass) / (Theoretical mass) x 100%
= (1.200 g) / (0.5714 g) x 100%
= 210 %
Using 4- methoxybenzaldehyde:

Mass of hydrazine = 0.1500 g

Mass of ethyl acetoacetate = 0.2500 g

Mass of 4-methoxybenzaldehyde = 0.2500 g

Mass of malononitrile = 0.1531 g

Mass of filter paper + watch glass = 18.2920 g

Mass of filter paper + watch glass + product = 19.1075 g

Mass of product = 0.8155 g

Melting point of product = 213-215 ℃

Based on above equation 1 mole of hydrazine reacts with 1 mole of ethyl acetoacetate, 1

mole of 4-methoxybenzaldehyde and 1 mole of malononitrile to produce 1 mole of

dihydropyrano-[2,3-c]pyrazoles. In the synthesis that carried out 3 mmole of hydrazine

reacts with 2 mmole of ethyl acetoacetate, 2 mmole of 4-methoxybenzaldehyde and 2 mmole

of malononitrile to produce 2 mmole of dihydropyrano-[2,3-c]pyrazoles. Ethyl acetoacetate,

4-methoxybenzaldehyde and malononitrile are limiting reagents.

Theoretical mass of dihydropyrano-[2,3-c]pyrazoles:

= No. of mole × Molecular mass

= 2 mmol × 281.2893 g/mol

= 0.5626 g

Percentage yield of dihydropyrano-[2,3-c]pyrazoles:

= (Actual mass)/(Theoretical mass) x 100%

= (0.8155 g)/(0.5626 g) x 100%

= 145 %
Discussion:

In this experiment dihydropyrano-[2,3-c]pyrazoles was synthesized using 4-

chlorobenzaldehyde and 4-methoxybenzaldehyde under ultrasound irradiation technique.

This was a green synthesis as water was used as solvent and no byproducts were formed. The

ultrasonic irradiation used also will increase the atom efficiency.

Altough the overall process can be said as green process unfortunately the percentage yield of

the product was not desirable. The percentage yield of dihydropyrano-[2,3-c]pyrazoles by

using 4-chlorobenzaldehyde and 4-methoxybenzaldehyde were 210 % and 145 %

respectively which shows that there is a lot of impurities present in the product. The melting

point also were far different from the literature values where the melting point of

dihydropyrano-[2,3-c]pyrazoles by using 4-chlorobenzaldehyde and 4-methoxybenzaldehyde

were 186 – 187 ℃ and 213-215 ℃ respectively. The theoretical melting point of

dihydropyrano-[2,3-c]pyrazoles by using 4-chlorobenzaldehyde and 4-methoxybenzaldehyde

were 218-220 ℃ and 208-210℃. This shows that there are a lot of errors that has been made

in this experiment.

The error is believed has been occur where the glasswares used were not washed properly

using acetones and also the final product contains water which greatly influenced the final

mass of the product. The product should be dried for several hours in the oven before being

measured its final mass. Besides that, the products also must be washed in cold water

frequently to remove the impurities present.

There are several prrecautions should be taken into account when handling the experiment.

safety goggles and gloves should be wore all the time when handling the experiment because

the chemicals used were toxic. Besides that, all the glasswares used must be rinsed and
washed with acetone to avoid any impurities present in the glassware to react with the

chemical process as what had happened in this experiment.

Conclusion:

Dihydropyrano-[2,3-c]pyrazoles was synthesized using 4-chlorobenzaldehyde and 4-

methoxybenzaldehyde under ultrasound irradiation. The percentage yield of dihydropyrano-

[2,3-c]pyrazoles by using 4-chlorobenzaldehyde and 4-methoxybenzaldehyde were 210 %

and 145 % respectively The melting point of dihydropyrano-[2,3-c]pyrazoles by using 4-

chlorobenzaldehyde and 4-methoxybenzaldehyde were 186 – 187 ℃ and 213-215 ℃

respectively.

Refrences:

ChemSpider, 2019. 2,4-Dihydropyrano[2,3-c]pyrazole | C6H6N2O | ChemSpider. [Online]

Available at: http://www.chemspider.com/Chemical-Structure.29336142.html
[Accessed 13 February 2019].

ScienceDirect, 2008. Ultrasound Irradiation - an overview | ScienceDirect Topics. [Online]

Available at: https://www.sciencedirect.com/topics/chemistry/ultrasound-irradiation
[Accessed 13 February 2019].

Science, D. o. C., 2019. UDEC 3134 Green Chemistry Lab Manual. In: Kampar: Universiti Tunku Abdul
Rahman, pp. 10-11.

Taylor&FrancisOnline, 2016. A FACILE ONE POT SYNTHESIS OF PYRANO[2,3-c]PYRAZOLE DERIVATIVES

UNDER MICROWAVE IRRADIATION. [Online]
Available at: https://www.tandfonline.com/doi/abs/10.1081/SCC-
120014044?src=recsys&journalCode=lsyc20
[Accessed 13 February 2019].

Technology, H. –. U., 2019. Sonochemical Reaction and Synthesis - Hielscher Ultrasonics GmbH.
[Online]
Available at: https://www.hielscher.com/sonochem_01.htm
[Accessed 13 February 2019].