Synthesis of 6-alyl-8-methoxy-3-propyl-1,3-benzoxazine and 4-alyl-6-

(dimethylamino) methyl-2-methoxy phenol from Eugenol through

Mannich Reaction and Antibacterial Activity Test

Sabarmin Perangin-angin and Sajidah Chairi

Department of Chemistry, Universitas Sumatera Utara, Medan, Indonesia

Keywords: Antibacterial, Eugenol, Mannich Reaction, 4-alyl-6-(dimethylamino)methyl-2-methoxy phenol, 6-alyl-8-

methoxy-3-propyl-1,3-benzoxazine

Abstract: 6-alyl-8-methoxy-3-propyl-1,3-benzoxazine and 4-alyl-6- (dimethylamino) methyl-2-methoxy phenol

compounds have been synthesized through the Mannich reaction. The 6-alyl-8-methoxy-3-propyl-1,3-

benzoxazine compound was synthesized by reacting eugenol, 37% formaldehyde, and propylamine under

conditions of reflux with ethanol solvents at 78ºC for 6 hours obtained compounds of 6,116 grams

(82.54%). The formation of 6-alyl-8-methoxy-3-propyl-1,3-benzoxazine compound characterized by FT-IR

obtained CN stretching vibration at wave number 1242.16 cm-1 and peak molecular ion m/e 247 through

GC-MS analysis. The 4-alyl-6- (dimethylamino) methyl-2-methoxy phenol compound was synthesized by

reacting eugenol, 37% formaldehyde, and 40% dimethylamine under reflux conditions with ethanol solvents

at 78ºC for 90 minutes and obtained compounds of 5,728 grams (86.39%). 4-alyl-6- (dimethylamino)

methyl-2-methoxy phenol compound characterized by FT-IR obtained CN and OH stretch vibrations at

wave numbers 1242.16 cm-1 and 3410.15 cm-1 and molecular ion peaks m/e 221 through GC-MS analysis.

Then the two antibacterial activity tests were carried out on the two compounds using Streptococcus mutans

and Escherichia coli bacteria with various concentrations of 10%, 20%, and 30%. The results obtained

showed that the 6-alyl-8-methoxy-3-propyl-1,3-benzoxazine and 4-alyl-6- (dimethylamino) methyl-2-

methoxy phenol compounds were classified as strong antibacterial.

1 INTRODUCTION

Eugenol is a phenolic compound that has several

functional groups such as allyl, hydroxide and

methoxy. With the existence of these functional

groups, the compound eugenol can be transformed

into a number of useful derivative compounds or to

be the basic material for the manufacture of other

compounds.

Some eugenol derivatives that have been carried

out are alkylation, addition, isomerization,

acetylation, esterification, polymerization, monoeter

cyclization and so on (Suryanto, 2008). Perangin-

angin (2019) have synthesized of 4-alil-6-

(hidroxymethyl)-2-methoxy phenol compounds from

eugenol through Mannich reaction followed

methylation with methyl iodide and substitution

using NaOH.

Eugenol is a class of phenylpropanoid chemical

compounds that have the potential for local

anesthetics that have been used medically by

dentists. There are phenol functional groups that

have antioxidant, anti-inflammatory, anti-allergic,

antithrombotic, antimicrobial and antineoplastic

activities (Soekardjo, 2000).

This ability is obtained from the lipophilic nature

of eugenol which can cause bacterial cell

membranes to undergo adhesion which causes

inhibited bacterial respiration. This will cause

disruption of ion transport in cells so that bacteria

experience death. In addition, phenol groups

contained in eugenol when attached to bacterial cells

will make bacteria undergo lysis, then die (Kumala,

2008).

Karanov et al. (1995) have synthesized eugenol

derivatives using formaldehyde and various types of

amines through the Mannich reaction. The new

compound formed is 2-methoxy-4- (2-propenyl) -6-

phenol-substituted aminomethyl derivative at

position 6 of eugenol which is known to have

activity as a plant growth regulator and pesticide.

Perangin-angin, S. and Chairi, S.

Synthesis of 6-Alyl-8-Methoxy-3-Propyl-1,3-Benzoxazine and 4-Alyl-6-(Dimetilamino)Methyl-2-Methoxy Phenol from Eugenol through Mannich Reaction and Antibacterial Activity Test.

DOI: 10.5220/0010205300002775

In Proceedings of the 1st International MIPAnet Conference on Science and Mathematics (IMC-SciMath 2019), pages 481-489

ISBN: 978-989-758-556-2

481

One example of a compound that has been

synthesized is 4-allyl-6- (dimethylamino) methyl-2-

methoxyphenol. The compound 4-allyl-6-

(dimethylamino) methyl-2-methoxyphenol can be

synthesized by reacting eugenol, dimethylamine, and

formaldehyde through the Mannich reaction.

Mannich reaction is a condensation reaction of

ammonia or primary amine or secondary amine and

formaldehyde with compounds containing acidic H

atoms bound to C or N atoms. In the Mannich

reaction, aldehyde condensation with ammonia or

primary amines or secondary amines will form the

Schiff base as an intermediate product.

The final product of the Mannich reaction is the

β-amino-carbonyl compound or the Mannich base

(Pine et al., 1988). Rudyanto et al. (2014)

synthesized benzoxazine and aminomethyl

compounds from eugenol and studied their

biological activity. Eugenol is reacted with

formaldehyde and methylamine following the

Mannich reaction. The benzoxazine compounds

obtained are then hydrolyzed to produce

aminomethyl derivatives. Furthermore, the

benzoxazine and aminomethyl compounds obtained

were tested for their biological activity using the

Brine Shrimp Lethality Test (BSLT), which is

testing the toxicity of a compound against Artemia

salina larvae.

Antibacterial activity test can be done by

diffusion and dilution methods. Disc diffusion test or

disk diffusion test is done by measuring the diameter

of the clear zone (clear zone) which is an indication

of the inhibitory response of bacterial growth by an

antibacterial compound in the extract. Requirements

for the number of bacteria for sensitivity test are

105-108 CFU / mL (Hermawan, 2007).

The diffusion method can be done in 3 ways

namely the cylinder method, the hole method and

the paper disc method. The hole method is to make a

hole in a solid agar that has been inoculated with

bacteria. The number and location of the holes are

adjusted to the purpose of the study, then the holes

are injected with the extract to be tested. After

incubation, bacterial growth was observed to see the

presence or absence of barriers around the hole

(Kusmayati, 2007).

Based on the above background, researchers are

interested in synthesizing benzoxazine and

aminomethyl compounds from eugenol through the

Mannich reaction using primary amines and

secondary amines to test their antibacterial activity.

2 MATERIALS AND METHOD

2.1 Synthesis of 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine

Compounds

Into the 100 mL three-neck flask with magnetic

stirrer included 28 mL ethanol and 4.8 g (0.03 mol)

eugenol were added. After dissolving, 37%

formaldehyde was added as much as 4 g (0.05 mol)

and 3.6 g (0.06 mol) propylamine followed by reflux

at 78

C for 6 hours. The mixture is cooled and

stirred with a magnetic stirrer for 24 hr.

Furthermore, the excess ethanol is evaporated with a

rotary evaporator. The results obtained were

analyzed with FT-IR and GC-MS

spectrophotometers.

2.2 Synthesis of 4-allyl-6-

(dimethylamino) methyl 2-methoxy

phenol Compound

Into the 100 mL three-neck flask with magnetic

stirrer included 28 mL ethanol and 4.8 g (0.03 mol)

eugenol were added. After dissolving, 37%

formaldehyde was added as much as 3.8 g (0.04

mol) and 5.6 g (0.05 mol) dimethylamine 40%

followed by reflux at 78

C for 90 minutes. The

mixture is cooled and stirred with a magnetic stirrer

for 24 hours. Furthermore, the excess ethanol is

evaporated with a rotary evaporator. The results

obtained were analyzed with FT-IR and GC-MS

spectrophotometers.

2.3 Preparation of Nutrient Agar Slant

About 7 g of NA was dissolved with 250 mL of

distillate water and sterilized in an autoclave at

121

C for 15 minutes.

2.4 Preparation of Medium Agar Slant

and Bacterial Culture Stock

The NA slant was prepared by adding 3 mL of NA

into test tube and placed it in the rack. Tilt the rack

onto solid surface so that the medium is slanted.

Allow the medium to harden in this position. The

culture was obtained from stock and taken with an

osse. This culture was incubated at 35

C for 18-24 h.

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2.5 Preparation of Mueller Hinton

Agar (MHA) Medium

Medium powder (19 g) was weighed into

erlenmeyer and dissolved with 500 mL of distillate

water sterilized in an autoclave at 121

C for 15

minutes.

2.6 Preparation of Bacterial Inoculum

Nutrient broth (3.25 g) was dissolved with 250 mL

of distillate water and sterilized in an autoclave at

121

C for 15 minutes. Furthermore, microbial

bacterial colony was taken from culture stock using

a sterilized osse. The culture was suspended into 10

mL of sterilized nutrient broth in the test tube and

incubated at 35

C for 3 h. The optical density of

bacterial was determined using spectrophotometer

UV-Vis at 580-600 nm.

2.7 Evaluation of Antibacterial Activity

The antibacterial activity of quaternary ammonium

salt was obtained by diffusion method. Paper disk (Ǿ

6 mm) had been soaked in various concentration of

quaternary ammonium salt (10, 20, and 30%). This

paper disk then placed on the agar medium that has

been cultured with E. coli and S. mutans. The

inhibition zone was measured using calliper (mm).

3 RESULTS AND DISCUSSION

3.1 Synthesis of 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine

Compounds

Eugenol used in this study is eugenol p.a E'Merck

with a purity level of ≥99%. The 6-allyl-8-methoxy-

3-propyl-1,3-benzoxazine compound obtained in the

form of a mixture of 6.116 grams (82.54%), in the

form of a blackish-brown liquid.

FT-IR spectroscopic data of 6-allyl-8-methoxy-

3-propyl-1,3-benzoxazine compound gives a

spectrum with vibrational peaks in the region of

wave number 3070.68 cm-1; 2947.23 cm-1; 2831.50

cm-1; 1597.06 cm-1; 1458.18 cm-1; 1242.16 cm-1;

1149.57 cm-1; 987.55 cm-1. The results of FT-IR

analysis of 6-allyl-8-methoxy-3-propyl-1,3-

benzoxazine compounds can be seen in Figure 1.

Figure 1: FT-IR of 6-allyl-8-methoxy-3-propyl-1,3-

benzoxazine compound.

The spectrum shown from FT-IR data supports

that the compound 6-ally-8-methoxy-3-propyl-1,3-

benzoxazine has a CN bond originating from the

benzoxazine group with the appearance of CN

stretching vibrations at wave number 1242,16 cm-1.

The absorption peak at wave number 3070.68 cm-1

shows the range of CH sp2, and the area of 2947.23

cm-1 and 2831.50 cm-1 shows the range of CH sp3

of alkyl which is reinforced by the peak at 1458.18

cm-1 for the group methylene (―CH2―) and C = C

aromatic are shown at wave number 1597.06 cm-1.

The vinyl group is shown at 987.55 cm-1. The peak

at 1149.57 cm-1 shows the stretch C-O-C of the

ether.

The 6-allyl-8-methoxy-3-propyl-1,3-benzoxazine

compound is obtained from eugenol through the

Mannich reaction, where eugenol is reacted with

iminium ions which were previously formed through

the reaction between formaldehyde and propylamine.

In the Mannich reaction of eugenol, the active

hydrogen from eugenol is replaced by the

propylaminomethyl group as an iminium ion. Then

the active nitrogen from the propylaminomethyl

group attacks the aluminum ion again to form an

oxazine ring by releasing propylamine. The Mannich

reaction was carried out under reflux conditions at a

temperature of 78 ° C for 6 hours using ethanol

solvent. The results of the eugenol, formaldehyde and

propylamine reactions produce 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine derivatives.

The mechanism of the 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine reaction can be seen in

Figure 2.

Synthesis of 6-Alyl-8-Methoxy-3-Propyl-1,3-Benzoxazine and 4-Alyl-6-(Dimetilamino)Methyl-2-Methoxy Phenol from Eugenol through

Mannich Reaction and Antibacterial Activity Test

483

. .

 H

. .

H H

. .

-OH

Formaldehid

Propilamin

Transfer proton

Ion iminium

C C

OCH

C C

OCH

C C

OCH

C C

OCH

C C

OCH

C C

OCH

+ H

-H

. .

C C

OCH

C C

OCH

C C

OCH

C C

OCH

- H

C C

OCH

6-alil-8-metoksi-3-propil-1,3-benzoksazin

Figure 2: Mechanism of 6-allyl-8-methoxy-3-propyl-1,3-

benzoxazine reaction.

The results of the analysis with GC-MS on6-

allyl-8-methoxy-3-propyl-1,3-benzoxazine

compounds obtained from the synthesis showed a

peak retention time of 34,491 minutes with a purity

of 88.52%. Mass chromatograms of compounds

synthesized by GC-MS can be seen in Figure 3.

Figure 3: GC-MS spectra of identified compounds.

IMC-SciMath 2019 - The International MIPAnet Conference on Science and Mathematics (IMC-SciMath)

484

The spectrum of compound 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine obtained is shown in Figure

Figure 4: Peak detection of identified compounds.

The peak with a retention time of 34.491 minutes

is a compound with the molecular formula

with a relative molecular mass of 247 g /

mol. Spectrum data show molecular ion peaks at m /

e 247 followed by fragmentation peaks at m / e 232,

218, 206, 191, 176, 161, 147, 133, 117, 107, 91, 77,

65, 42, 41, and 28 where this value corresponds to

the relative molecular weight (Mr) of the

synthesized 6-ally-8-methoxy-3-propyl-1,3-

benzoxazine compound. Fragmentation patterns can

be seen in Figure 5.

Figure 5: Fragmentation pattern of synthesized compound.

3.2 Synthesis of 4-allyl-6-

(dimethylamino) compound

methyl-2-methoxy phenol

Eugenol used in this study is eugenol p.a E'Merck

with a purity level of ≥99%. Compound 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol obtained

in the form of a mixture of as much as 5.728 grams

(86.39%), in the form of a blackish brown liquid.

FT-IR spectroscopy data of 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol

compound gives a spectrum with vibrational peaks

in the region of wave number 3410.15 cm-1;

3070.68 cm-1; 2947.23 cm-1; 2900.94 cm-1;

2831.50 cm-1; 1597.06 cm-1; 1465.90 cm-1;

1242.16 cm-1; 1149.57 cm-1; 987.55 cm-1. The

results of FT-IR analysis of 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol

compounds can be seen in Figure 6.

Figure 6: FT-IR of 4-allyl-6- (dimethylamino) methyl-2-

methoxy phenol compound.

The spectrum shown from FT-IR data supports

that the 4-allyl-6- (dimethylamino) compound

methyl-2-methoxy phenol formed has a CN bond

originating from the dimethylaminomethyl group

with the emergence of CN stretching vibrations at

the wave number 1242.16 cm- 1 The absorption

peak at wave number 3410.15 cm-1 shows the O-H

vibrations. The absorption peak at wave number

3070.68 cm-1 shows the range of C-H sp2 and in the

area of 2947.23 cm-1; 2900.94 cm-1 and 2831.50

cm-1 shows the CH sp3 range of alkyl reinforced

with a peak at 1465.90 cm-1 for the methylene

group (―CH2―) and C = C aromatic shown at

wave number 1597.06 cm-1. The vinyl group is

shown at 987.55 cm-1. The tape at 1149.57 cm-1

shows the stretch C-O-C of the ether.

The 4-allyl-6- (dimethylamino) methyl-2-

methoxy phenol compound is obtained from eugenol

through the Mannich reaction, where eugenol is

reacted with iminium ions which were previously

Synthesis of 6-Alyl-8-Methoxy-3-Propyl-1,3-Benzoxazine and 4-Alyl-6-(Dimetilamino)Methyl-2-Methoxy Phenol from Eugenol through

Mannich Reaction and Antibacterial Activity Test

485

formed through the reaction between formaldehyde

and dimethylamine. In the Mannich reaction, the

active hydrogen from eugenol is replaced by the

dimethylaminomethyl group. The Mannich reaction

was carried out under reflux conditions at a

temperature of 78°C for 90 minutes using ethanol as

a solvent. The results of the eugenol, formaldehyde

and dimethlamine reactions produce the 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol

derivative.

The reaction mechanism of the 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol

compound can be seen in Figure 7.

Dimetilamin

. .

H CH

Transfer proton

Ion iminium

-OH



Formaldehid

. .

H CH

C C

OCH

C C

OCH

4-alil-6-(dimetilamino)metil-2-metoksi fenol

C C

OCH

C C

OCH

C C

OCH

C C

OCH

+ H

-H

. .

Figure 7: Reaction mechanism of the 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol.

Results of analysis with GC-MS on 4-allyl-6-

(dimethylamnino) methyl-2-methoxy phenol

compounds obtained from the synthesis showed a

peak retention time of 29,650 minutes with a purity

of 86.54%. Mass chromatograms of compounds

synthesized by GC-MS are shown in Figure 3.8.

Figure 8: GC-MS spectra of identified compounds.

The spectrum of the compound 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol obtained

was shown in Figure 9.

Figure 9: Peak detection of identified compounds.

The peak with a retention time of 29,650 minutes

is a compound with the molecular formula

with a relative molecular mass of 221 g /

mol. Spectrum data show the peaks of molecular

ions at m / e 221 followed by fragmentation peaks at

m / e 204, 190, 176, 161, 147, 133, 117, 107, 91, 77,

58, 44, 39, and 28, where this value corresponds to

the relative molecular weight (Mr) of the 4-allyl-6-

(dimethylamino) compound synthesized methyl-2-

methoxy phenol. Fragmentation patterns can be seen

in Figure 10.

IMC-SciMath 2019 - The International MIPAnet Conference on Science and Mathematics (IMC-SciMath)

486

Figure 10: Fragmentation pattern of 4-allyl-6-

(dimethylamino) compound.

3.3 Antibacterial Activity Test

Antibacterial activity test of 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine compound and 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol

compound from the synthesis results in the form of

mixture using Streptococcus mutans and Eschericia

coli can be seen in Table 1 and 2.

Table 1: Tests for antibacterial activity against 6-allyl-8-

methoxy-3-propyl-1,3-benzoxazine compounds.

Treatment

Disc Diameter

(mm)

Clear Zone Diameter

(

)

S. mutans E. coli

10%

6 18.5 21

20%

6 33 21

30%

6 33 14

Table 2: Tests for antibacterial activity against 4-allyl-6-

(dimethylamino) methyl-2-methoxy phenol compounds.

Treatment

Disc Diameter

(mm)

Clear Zone Diameter

(

)

S. mutans E. coli

10% 6 12 18

20% 6 19 16

30% 6 17 14

Data on antibacterial activity test results showed

that there were antibacterial activities for both

Streptococcus mutans and Escherichia coli bacteria

in 6-allyl-8-methoxy-3-propyl-1,3-benzoxazine and

4-allyl-6- (dimethylamino) methyl-compound 2-

methoxy phenol. This is because the 6-allyl-8-

methoxy-3-propyl-1,3-benzoxazine compound and

the 4-allyl-6- (dimethylamino) methyl-2-methoxy

phenol compound have a nitrogenous base group.

This base group will react with amino acids that

make up the cell wall and bacterial DNA which are

the main constituents of the cell nucleus. This

reaction results in changes in the structure and

composition of amino acids that cause changes in

genetic balance so that the bacterial DNA will be

damaged. Cell damage to bacteria will eventually

make the bacteria unable to metabolize so that it will

also undergo lysis. Thus, the bacteria will become

inactive and destroyed (Gunawan, 2008).

In the antibacterial activity test of 6-allyl-8-

methoxy-3-propyl-1,3-benzoxazine compound

against Streptococcus mutans, the antibacterial

activity is stronger than eugenol. This is shown by

the highest clear zone diameter at concentrations of

20% and 30%, which is 33 mm while in eugenol the

highest clear zone diameter is 18 mm at a

concentration of 10%.

In the antibacterial activity test of 6-allyl-8-

methoxy-3-propyl-1,3-benzoxazine compound

against Escherichia coli, the highest clear zone

diameter at concentrations of 10% and 20% is 21

mm and has decreased at a concentration of 30%

that is equal to 14 mm. In the antibacterial activity

test of 4-allyl-6- (dimethilamino) methyl-2-methoxy

phenol compound against Streptococcus mutans the

highest clear zone diameter was obtained at a

concentration of 20% at 19 mm and decreased at a

concentration of 30% at 17 mm, whereas, against

Escherichia coli the highest clear zone diameter at a

concentration of 10% is 18 mm and has decreased at

20% and 30% that is 16 mm and 14 mm.

Based on the test results of antibacterial activity



against bacteria Streptococcus mutans and

Escherichia coli obtained inhibitory zone diameters

Synthesis of 6-Alyl-8-Methoxy-3-Propyl-1,3-Benzoxazine and 4-Alyl-6-(Dimetilamino)Methyl-2-Methoxy Phenol from Eugenol through

Mannich Reaction and Antibacterial Activity Test

487

that have fluctuated and not proportional to the

concentration of the compound.

Elifah (2010) suggested that the diameter of the

inhibition zone does not always increase in

proportion to the increase in antibacterial

concentration. This can occur because of differences

in the speed of diffusion of antibacterial compounds

on agar media. Different types and concentrations of

antibacterial compounds give different inhibitory

zone diameters for a certain period of time.

Irregularity in the diameter of the zone of inhibition

of the growth of test bacteria is at the time of

unequal disk drying. Therefore, it causes a inhibitory

zone at the highest concentration to decrease. Disk

which has long drying time, when it is placed on top

of the bacterial hatching media, the area of the

inhibitory zone is small, this zone is formed from

extracts diffused from the disk to the agar media. On

disks with only a short drying time, when placed on

top of the bacterial hatchery media, the extract

which is still attached immediately spreads around

the disk and quickly diffuses to the media so as to

form a larger inhibitory zone.

Sinarsih (2016) suggests that the presence of

unstable antibacterial performance at high

concentrations is likely due to compounds in general

having a limited ability in bioactivity. So that at

increasing concentrations certain compounds do not

provide a significant increase in response or not

significantly different.

The strength of antibacterial activity can be seen

from the inhibitory zone formed. According to

(Aleksandra et al., 2017) said that antibacterial

activity was classified to be 3 groups. There were

strong that produced inhibition zone diameter at 8

mm, medium activity that produced inhibition zone

at 7-8 mm, while weak activity that produced

inhibition zone diameter less than 7 mm. Thus 6-

allyl-8-methoxy-3-propyl-1,3-benzoxazine

compound and 4-allyl-6- (dimethylamino) methyl-2-

methoxy phenol compounds have relatively strong

antibacterial activity.

4 CONCLUSION

Synthesis of 6-allyl-8-methoxy-3-propyl-1,3-

benzoxazine compound obtained from eugenol

through the Mannich reaction, where eugenol is

reacted with iminium ions which were previously

formed through the reaction between formaldehyde

and propylamine. The results obtained were 6.116

grams (82.54%) compound of 6-allyl-8-methoxy-3-

propyl-1,3-benzoxazine. The formation of 6-allyl-8-

methoxy-3-propyl-1,3-benzoxazine compound is

characterized by the appearance of C-N stretching

vibrations at wave number 1242.16 cm-1

Synthesis of 4-allyl-6- (dimethylamino) methyl-

2-methoxy phenol compound obtained from eugenol

through the Mannich reaction, where eugenol is

reacted with iminium ions which were previously

formed through the reaction between formaldehyde

and dimethylamine. The results obtained were 5,728

grams (86.39%) of the 4-allyl-6- (dimethylamino)

compound methyl-2-methoxy phenol. The formation

of 4-allyl-6- (dimethylamino) compound methyl-2-

methoxy phenol is characterized by the appearance

of C-N stretching vibrations at wave number

1242.16 cm-1 and O-H vibrations at wave number

3410.15 cm-1

The 6-allyl-8-methoxy-3-propyl-1,3-benzoxazine

compound and the 4-allyl-6- (dimethylamino)

methyl-2-methoxy phenol compound exhibit

antibacterial activity that is classified as strong

against S. mutans and E bacteria .coli. This is

indicated by the diameter of the clear zone produced

which is more than 8 mm so that both compounds act

as antibacterials that are classified as strong.

ACKNOWLEDGEMENTS

Author would like to thank to organic chemistry

laboratory faculty of mathematics and natural

sciences University of Sumatera Utara.

REFERENCES

Aleksandra, O.B., N, D.Z., Rzepkowska, A., Ko,D., 2017.

Comparison of Antibacterial Activity of Lactobacillus

plantarum Strains Isolated from Two Different Kinds

of Regional Cheeses from Poland : Oscypek and

Korycinski Cheese.

Gunawan, I.W.A. 2008. Isolasi dan Identifikasi Senyawa

Terpenoid yang Aktif Antibakteri pada Herba Meniran

(Phyllanthus Niruri Linn). Jurnal Kimia2 (1): 31-39.

Hermawan. A., 2007. Pengaruh Ekstrak Daun Sirih (Piper

betle L.) terhadap Pertumbuhan Staphylococcus

aureus dan Escherichia coli Dengan Metode Difusi

Disk, Artikel Ilmiah, Fakultas Kedokteran Hewan,

Universitas Airlangga Surabaya.

Karanov, E., L. Iliev, V. Alexieva, G. Ts. Georgiev, N. T.

Thang, and L. Natova, 1995, Synthesis and

Plant Growth Regulating Activity of some Novel 2-

Methoxy-4-(1-Or2 Propenyl)-6-Substituted Phenol,

Journal Plant Physiology,21(4),39- 47.

IMC-SciMath 2019 - The International MIPAnet Conference on Science and Mathematics (IMC-SciMath)

488

Kumala, Shirly, dan Dian Indriani. 2008. Efek Antibakteri

Ekstrak Etanol Daun Cengkeh (Eugenia aromaticum

L). Jurnal Farmasi Indonesia , 4(2):82-86.

Kusmayati, Agustini., 2007. Uji Aktivitas Senyawa

Antibakteri dari Microalga (Prorpyridium cruentum).

Jurnal Biologi Universitas Atmajaya. Yogyakarta.

Perangin-angin, S., 2019. Synthesis of 4-Alil-6-

(Hidroxymethyl)-2-Methoxy Phenol Compounds from

Eugenol Through Mannich Reaction Followed

Methylation with Methyl Iodide and Substitution

Using NaOH. JCNaR.01,75-85

Pine, S. H., J. B. Hendrikson, D. J. Cram, dan G. S.

Hammond, 1988, Kimia Organik, edisi IV,

terjemahan R. Joedodibroto dan S. W. P.

Hadiwidjoyo, ITB, Bandung, 152-153, 325-326

Rudyanto, M., Ekowati, J., Widiandani, T., Honda, T.

Synthesis and brine shrimp lethality test of some

benzoxazine and aminomethyl derivatives of eugenol

International Journal of Pharmacy and Phamaceutical

Sciences.2014; 6(2): 465-467

Sinarsih, N. K., Rita, W. S., Puspawati, N. M ., 2016. Uji

Efektifitas Ekstrak Daun Trembesi (Samanea saman

(jacq.) Merr) Sebagai Antibakteri Escherichia coli dan

Staphylococcus aureus. Journal of Applied Chemistry;

4(2).

Soekardjo, B. dan Sondakh, R. 2000. Hubungan Struktur-

Aktivitas Obat Antiinfeksi, dalam :Kimia Medisinal,

Siswandono dan B. Soekardjo (eds.), ed. 2,

jil.2,Airlangga University Press, Surabaya, 21

Synthesis of 6-Alyl-8-Methoxy-3-Propyl-1,3-Benzoxazine and 4-Alyl-6-(Dimetilamino)Methyl-2-Methoxy Phenol from Eugenol through

Mannich Reaction and Antibacterial Activity Test

489