Green Synthesis of 4-Hydroxy-4-Methoxychalcone by Grinding

Techniques

Elfi Susanti V. H. and Sri Mulyani

The Chemical Education Study Program of FKIP Universitas Sebelas Maret, Surakarta, Indonesia

Keywords: Green Synthesis, 4-Hydroxy-4-Methoxychalcone, Grinding Techniques

Abstract: The synthesis of the 4-hydroxy-4-methoxychalcone has been synthesized by grinding techniques. This

compound was synthesized by reacting 4-hydroxybenzaldehyde with 4-methoxy acetophenone using NaOH

catalyst in a mortar for 30 minutes at room temperature. The reaction product was monitored by TLC and then

recrystallized from ethanol, and golden yellow crystals were obtained. Characterization of synthesized

compounds with

H-NMR and

C-NMR.

H-NMR (CDCl3, δ ppm): 3,86 (3H, s, H-OCH

), 6.86 (2H, d, J=10,

Ar-H), 7,07 (2H, d, J=5 Hz, Ar-H), 7,66 (1H, d, J=15, H-Cα), 7,75 (1H, d, J=7, H-Cβ), 7,73 (2H, d, Ar-H),

8,14 (2H, d, J=9 Hz, Ar-H), 10,09 (1H, s, UH-OH).

CNMR (CDCl

, δ, ppm): 187,28 (C=O), 163.04 (C4),

160,01 (C4), 143,70 (C=C-β), 130,95 (C2 dan C6), 130,82 (C2 dan C6), 130,77 (C1), 125,98 (C1), 118,44

(C=C-α), 115,84 (C3 dan C5), 113,99 (C3 dan C5), 55,57 (-OCH

). The results of

H-NMR and

C-NMR

characterization showed that the synthesized compound had been formed.

1 INTRODUCTION

Chalcone (1,3-diphenyl propenone) is an intermediate

agent in synthesising various heterocyclic compounds

(Patil, et al., 2009). Chalcone can be synthesized

using Claisen-Schmidt condensation, a condensation

reaction between aromatic aldehydes and aromatic

ketones to form α, β-unsaturated ketones. Claisen-

Schmidt condensation can occur in an acid or base.

The use of acid catalysts in condensation reactions

(e.g., HCl, BF

, B

) generally gives low yields (10-

40%) (Patil, et al., 2009). The KOH catalyst in the

synthesis reaction of chalcone through the Claisen-

Schmidt reaction obtained an 88-94% yield (Zangade,

et al., 2011). The use of Ba(OH)

in the synthesis of

chalcone derivatives was obtained with a yield of 88-

98% (Rateb, Zohdi, 2009), and the NaOH catalyst

obtained a yield of 90-96% (Mogilaiah, et al., 2010).

The Claisen-Schmidt reaction in the synthesis of

chalcone with NaOH catalyst gave better results

(yield 93-98%) than using KOH, NaOAc, and

OAc (yield 81-85%) (Rahman, et al., 2012).

Moreover, the Claisen-Schmidt reaction is essential in

synthetic organic chemistry. The synthesis of

chalcone through the Claisen-Schmidt condensation

reaction has been widely used (Prasad, et al., 2008).

Susanti (Susanti, et al., 2012 and 2014) have

synthesized hydroxy chalcone from hydroxy

acetophenone and methoxy benzaldehyde through

conventional Claisen-Schmidt condensation using

ethanol solvent. Their results revealed that the

formation of hydroxy chalcone compounds requires a

strong base (50%), a long reaction time (24 hours),

and a low yield (40-70%). Thus, this current research

will develop a new chalcone synthesis design through

the green chemistry approach, namely solvent-free

synthesis using grinding techniques (Susanti, et al.,

2014).

The grinding technique in synthesis is the

development of chalcone synthesis, which is very

profitable because it uses very simple equipment,

namely pestle and mortar. Chalcone synthesis was

modified using grinding techniques to synthesize

chalcone compounds from 2-acetyl-1-naphthol and

benzaldehyde (Zangade, et al., 2011). Meanwhile,

synthesized chalcone with this technique running

without solvent, short reaction time (4-8 minutes),

and high yields (84-95%). Grinding techniques have

also been used to synthesize chalcone from

cyclohexanone and benzaldehyde, giving 96-98%

yield. Susanti have also synthesized three derivatives

of hydroxy chalcone compounds using this technique

and yielded 70-84% (Susanti, et al., 2014). However,

this grinding technique has not been performed to

V. H., E. and Mulyani, S.

Green Synthesis of 4-Hydroxy-4’-Methoxychalcone by Grinding Techniques.

DOI: 10.5220/0010801900003317

In Proceedings of the 2nd International Conference on Science, Technology, and Environment (ICoSTE 2020) - Green Technology and Science to Face a New Century, pages 167-170

ISBN: 978-989-758-545-6

167

synthesize the chalcone derivative of 4-

methoxyacetophenone with substituted

benzaldehyde. In this study, a new chalcone

derivative of 4-methoxyacetophenone and 4-

hydroxybenzaldehyde will be synthesized.

2 RESEARCH METHODS

2.1 Materials

The materials used in this study had analytical grade

quality from E-Merck, including 4-

hydroxybenzaldehyde, 4-methoxyacetophenone,

sodium hydroxide, hydrochloric acid, sulfuric acid,

acetone, ethyl acetate, ethanol, n-hexane, chloroform,

methanol, dichloromethane, and anhydrous sodium

sulfate.

2.2 Instrumentation

Instruments in this study were laboratory glassware,

analytical scales (Libror EB330 Shimadzu), magnetic

stirrer, chromatography column, reflux device,

desiccator, magnetic stirring plate, Buchi evaporator,

254 nm UV lamp, Whatman paper no 1, test tube,

callipers, magnetic resonance spectrometer Proton

core (1H-NMR, 500 Mhz) and carbon (13C-NMR,

125 MHz), and JEOL-MY500.

2.3 Procedure

The chalcone compound was synthesized by grinding

4-methoxyacetophenone with 4-bromobenzaldehyde

in a mortar and pestle at room temperature for several

minutes. The completeness of the reaction was

monitored by Thin Layer Chromatography (TLC).

The reaction mixture was then diluted with cold

water, neutralized with a cold solution of HCl 10%

(v/v), then filtered. Purification was carried out by

employing recrystallization. The synthetic products

were then characterized using

H- and

C-NMR

spectrometers.

3 RESULTS AND DISCUSSION

3.1 Synthesis of Chalcone by Grinding

Techniques

The synthesis of chalcone compounds using grinding

techniques was carried out by grinding 4-

methoxyacetophenone, 4-hydroxybenzaldehyde, and

solid NaOH in mortar. This grinding process was

performed at room temperature for 30 minutes. In this

process, friction energy was generated from local heat

due to collisions between reactants, which accelerate

the reaction to form products. The monitoring of the

results of the synthesized compounds was conducted

using Thin Layer Chromatography. The synthesis

results in yellow crystals as much as 0.8 g (32.5%

yield) were obtained after the recrystallization

process using ethanol. Characterization of chalcone

compounds was done using a

H-NMR spectrometer.

The

H-NMR spectrum of the NMR chalcone

compounds, as presented in Figure 1, showed 14

protons in the synthesized compound. The absorption

peak at the chemical shift (δ) of 3.85 ppm was thought

to be a proton signal from the methoxy group with a

singlet and 3-integrated appearance. The singlet

appearance indicates that no neighboring protons

were coupling these protons. The absorption at 6.84

ppm chemical shift with a doublet's appearance was a

signal from the protons from C3 and C5 in the

aromatic ring B. This doublet appearance occurred

because the protons in C3 and C5 were one

neighbouring proton.

The chemical shift at 7.06 ppm was the proton

signal owned by C3 'and C5' (aromatic ring A). This

assumption was strengthened because the peak at 7.06

ppm had a doublet appearance, revealing that the

protons C3' and C5' had the same environment, one

neighbouring proton. A peak with a similar

appearance also occurred at the chemical shift of 7.73

ppm (the protons in C2 and C6) and 8,14 ppm (the

protons in C2' and C6'). Olefin protons of α, β-ketone

unsaturated were observed at the chemical shift of

7.64 and 7.75 ppm with coupling constants J = 9 and

15 Hz, respectively. It revealed that the chalcone

formed had a trans structure. The peak at 10.09 ppm

has a singlet appearance which is the unprotected

absorption of hydroxy protons due to the induction of

the electronegative O atom. The results of chalcone

H-NMR spectral analysis are presented in Table 1.

Figure 1a.

H -NMR spectrum of chalcone

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Figure 1b.

H -NMR spectrum of chalcone

Table 1. Results of the

H -NMR spectral analysis of

chalcone 1

The structural characterization of the synthesized

compounds was further strengthened by the

C-NMR

analysis (Figure 2), which exhibited 12 signals and

indicated the presence of 12 different carbons. The

absorption for methoxy carbon was observed at a

chemical shift of 55.65 ppm. The carbonyl band

(C=O) was shown at a far chemical shift (deshielding

area), at chemical shift 187.28 ppm. It is following

Mostaher who asserted that the carbonyl carbon from

chalcone usually appears in the area of 170-194.6

ppm (Mostahar et al., 2007). The carbon is bonded

directly to the O atom, which has a large

electronegativity so that the electrons around the C

atom increasingly unprotect the nucleus of the C atom

due to being attracted by the O atom.

Figure 2a.

C-NMR Spectrum of chalcone

Figure 2b.

C-NMR Spectrum of chalcone

Carbon with the same environment will appear

as one peak in the 113.9 ppm chemical shift, which is

the absorption of C3 dan C5. The same thing

happened to absorption at 115.8 ppm (C3 and C5),

130.8 ppm (C2 and C6), and 114,09 (C2 and C6).

The absorption of Cα was observed at a chemical shift

of 119.4 ppm, while Cβ was at 143.7 ppm. The C-β

peak appeared more downfield than the C-α atom. It

is aligned with Mostahar et al. research (2007), which

uncovered that the C-β absorption of chalcone

compounds appeared in a more remarkable chemical

shift than C-α. In detail, the results of the chalcone

C-NMR spectral analysis are presented in Table 2.

Table 2. Results of the

C-NMR spectral analysis of

chalcone

Chemical

Shift δ

(ppm)

Appea

rance

Coupling

Constants

J (Hz)

Number and

Type of Proton

3,86 singlet 3H, -OCH

6,84

doublet

2H at C3 & C5

7,07

doublet

2H at C3' & C5'

7,66

doublet

1H at C-α

7,73

doublet

7,5

2H at C2 & C6

7,75

doublet

1H at C-β

8,14 double

9 2H at C2' & C6'

10,09

ingle

1H at OH

Chemical Shift δ (

m) T

e of Carbon

187,28 C=O

163,04 C4'

160,01 C4

143,70 C-β

130,95 C2' dan C6'

130,82 C2 dan C6

130,77 C1'

125,98 C1

118,44 C-α

115,84 C3 dan C5

113,99 C3' dan C5'

55,57 C-OCH

Green Synthesis of 4-Hydroxy-4’-Methoxychalcone by Grinding Techniques

169

Based on the

H- and

C-NMR analysis results

that have been carried out, it could be stated that

chalcone, namely 4-hydroxy-4-methoxychalcone,

has been formed from the results of the Claisen-

Schmidt condensation process between 4-

methoxyacetophenone and 4-hydroxybenzaldehyde.

The synthesized product was a yellow crystal. The

chalcone formation reaction was assumed to follow

the condensation aldol reaction mechanism. The

reaction started from an acid-base reaction, where the

base took a proton from the α carbon of 4-

methoxyacetophenone to form an enolate ion, which

stabilized by resonance. The nucleophilic addition of

carbanions from 4-methoxyacetophenone then

occurred to the carbonyl carbon of 4-

bromobenzaldehyde, followed by releasing water

molecules with acids' help form double bonds (Figure

3).

Synthesis of chalcone using grinding techniques

is a strategic breakthrough because it considers the

principle of green chemistry, namely reducing the use

of solvents in the synthesis process. Solvents in the

synthesis of many compounds are toxic and cause

environmental problems. Therefore, it is vital to

develop a method of compound synthesis without a

solvent. In the grinding process, all reactants are

crushed in a mortar. The collision between the

reactants occurs and creates friction energy from local

heat, accelerating the reaction to form chalcones.

Figure 3. Reaction Mechanism in Chalcone Synthesis

4 CONCLUSION

The development of environmentally friendly

synthesis methods needs to be developed

continuously. The use of grinding techniques in

chalcone synthesis is a route with great potential to be

developed. Researchers have successfully synthesised

4-hydroxy-4'-methoxy-chalcone by reacting 4-

methoxyacetophenone and 4-hydroxybenzaldehyde

through a green chemistry approach with grinding

techniques. The study of this compound application

as an active antibacterial compound is ongoing.

ACKNOWLEDGEMENTS

I would like to thank the Universitas Sebelas Maret,

for provided funding for implementing this research.

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