EUGENOL THÀNH PHẦN HÓA HỌC CỦA ĐÁNH RĂNG VÀ MỘT SỐ CHẤT KHỬ MÙI CÓ CÔNG DỤNG CAO

VIETNAM NATIONAL UNIVERSITY, HA NOI VNU UNIVERSITY OF SCIENCE FACULTY OF CHEMISTRY NGUYEN THI THU NGOC EUGENOL – CHEMICAL COMPOSITION OF CLOVES AND SOME DERIVATIVES WITH HIGH USE Instructor Dr Nguyen Hoang Yen Ha Noi – 2021 2 ACKNOWLEDGEMENT First of all, I would like to express my gratitude and sincere thanks to Dr Nguyen Hoang Yen has enthusiastically helped and oriented his way of thinking and working scientifically Those are very valuable suggestions not only in the process of making thi.

VIETNAM NATIONAL UNIVERSITY, HA NOI

VNU UNIVERSITY OF SCIENCE

FACULTY OF CHEMISTRY

***

NGUYEN THI THU NGOC

EUGENOL – CHEMICAL COMPOSITION OF CLOVES

AND SOME DERIVATIVES WITH HIGH USE

Instructor: Dr Nguyen Hoang Yen

Ha Noi – 2021

ACKNOWLEDGEMENT

First of all, I would like to express my gratitude and sincere thanks to Dr Nguyen Hoang Yen has enthusiastically helped and oriented his way of thinking and working scientifically Those are very valuable suggestions not only in the process of making this thesis, but also a stepping stone for me in the process of studying and setting up a career later

Next, I would like to thank my family and friends, who are always willing to share and help in study and life Hope we will stick together forever

Wish the best will always accompany everyone

Thank you for all

Student,

Nguyen Thi Thu Ngoc

CONTENT

ACKNOWLEDGEMENT 2

CONTENT 3

SIGNAL TABLE OF ABBREVIATIONS 4

INTRODUCTION 5

CHAPTER 1: OVERVIEW 6

1 Overview of clove 6

1.1 Scientific name 6

1.2 Description of clove 6

1.3 Distribution 7

1.4 Plant and harvest 7

1.5 Parts used to separate essential oils 7

2 Effect 7

3 Chemical composition of clove 8

4 Eugenol 10

CHAPTER 2: EUGENOL EXTRACT FROM CLOVE OIL 11

CHAPTER 3: SOME DERIVATIVES OF EUGENOL 13

1 Isoeugenol 13

2 Zinc oxyde eugenol 14

3 Some derivatives of eugenol 15

CHAPTER 4: FUTURE RESEARCH DIRECTIONS 16

REFERENCES 17

SIGNAL TABLE OF ABBREVIATIONS

INTRODUCTION

Essential oils are an extremely valuable gift that nature bestows on humans Each

essential oil contains tens to hundreds of different natural compounds, so essential oils

are being considered as an excellent choice in therapy, aromatherapy and beauty One of

the essential oils that is in great demand today is Syzygium aromaticum (clove) oil

The main component of clove is eugenol (2-methoxy-4-allylphenol) It makes up

about 76.8% of the composition of clove essential oil and has a very pleasant

smell Eugenol has many uses:

Eugenol in dental medicine is used as a toothache, with oxide e zinc Eugenol

cement forming adhesive substance used for temporary fillings

In the food industry, eugenol is used as a raw material for the synthesis of

vanillin

From Eugenol synthesized methyl e ugenol, a substance that attracts insects to

gather in one place to easily trap them , and synthesize a number of substances that

stimulate plant growth

In addition, eugenol also plays an important role in the cosmetic industry

In this yearbook, we want to clarify three things:

- Extract of Eugenol from Clove

- Synthesis of some derivatives of eugenol

- Preliminary exploration of the biological effects of eugenol and other substances

CHAPTER 1: OVERVIEW

1 Overview of cloves

1.1 Scientific name:

Syzygium aromaticum (L.) Merrill &L M Perry

Tên đồng nghĩa: Eugenia caryophyllata Thunb

Cloves are also known as Cong cloves, Hung Tu Huong, and Dinh

Tu

Scientific classification:

Gender: Plantae Set: Myrtales Family: Myrtaceae

Genus: Eugenia Species: E.caryophyllata Thunb

1.2 Description of clove:

Figure 1 Cloves

+ Small tree, 10-12m tall Leaves opposite, oval , pointed, not falling

Figure 2 Clove flower

+ Flowers grow into small cymbal and branched at the top of branches, flowers consist of 4 thick sepals, bright red when ripe, 4 pink petals, falling early when blooming, lots of stamens

+Fruits are long berries, surrounded by sepals, usually containing only one seed 1

1.3 Distribution:

Cloves are native to the Moluccas Islands (Indonesia) and are produced mainly in Tanzania, Malysia, Indonesia, the Zanziba Islands, Pemba (Tandania), Madagascar

Our country used to import cloves Recently, we have tried to migrate a few trees but have not developed and are currently losing seed first.1 1.4 Plant and harvest:

Planted with seeds

The 5th or 6th year will flower, but the highest harvest is in the 20th year Depending on the region, each year will be harvested 1-2 times, when the buds begin to red

Pick flowers by hand while still in the bud stage, separating the stem and flower buds Hang or dry until it turns brown

Do not wait until the fruit is harvested before harvesting because then the quality is much worse when in bud form

1.5 Parts used to separate essential oils Oleum Caryophyllorum commercial name is clove oil, is distilled from flower buds, flower stalks and leaves

90-95% of clove leaf essential oil is distilled from the leaves, usually only poor quality flower buds are used to store the essential oil

2 Effect

Since ancient times, the emperors of the Han Dynasty used to make their followers chew clove leaves to freshen their breath Found since ancient times, has become a valuable commodity and has caused a fierce competition between the Portuguese, Dutch and British for the position of the spice trading market Because Clove flower has been considered a precious spice to process curry powder along with turmeric, ginger, black pepper, chili Clove flowers are also used to marinate aromatic tobacco and make liqueurs, perfume Today, in many Southeast Asian countries,

people still have the custom of using clove flowers for the purpose of freshening their breath, fighting bad breath and preventing diseases during outbreaks

In our country, Hai Thuong Lan Ong also used clove flowers in combination with cinnamon, raw ginger, bone pain, bone anise, seashells, water shells, chau chau leaves, cactus latex, purple mulberry leaves

jasmine leaves, vajra leaves, buying leaves, blood senses, turmeric, chyme seeds, dog blood seeds, pomelo leaves, star fruit mistletoe leaves, equal amounts of 10-20g, pound hot stars and apply to cure sprains , luxation 2

Eugenol is the main component of the essential oil extracted from Clove flower buds It was the first component of an essential oil that has been shown to act as an antiseptic and pain reliever in dentistry that is still used today Eugenol is also an important agent in cosmetics and food flavoring Its properties towards various radicals such as DPPH, ABTS, superoxide and azide, hydroxyl and aloperoxyl radicals have been reported It has been shown to inhibit prostaglandin synthesis-7 and COX-2 inhibition value IC50 is 129 mol 7 ( The IC50 value of was used to compare the potentials of the two antagonists)

In carcinogenicity testing of different groups in CD-1 and F344 mice Eugenol did not bind to the tumor In the "skin paining" study by Van Duuren and Gold-schmidt, Eugenol effectively contributed to the inhibition

of benzopyrene, a skin carcinogen Eugenol can inhibit DMBA-generine oil-causing cancer by about 84% (DMBA is a chemical commonly used to induce experimental breast cancer.) In the Bl6 Eugenol therapy resulted in

a significant reduction in tumor growth (p = 0.0057), a nearly 40%

reduction in tumor size, and a 19% increase in mean time to endpoint Many scientific evidences have proven that Eugenol has cytotoxic potential, which can be used to treat human cancer cells 8

3 Chemical composition of cloves

Clove essential oil with content of 15-20% in flower buds, 5-6 % in flower stalks and 2-3 % in leaves.1

The composition of clove essential oil 9 is listed in the following table:

Compound Percent

Table 1.Chemical composition of clove essential oil

Density: d15 = 1.043 – 1.068 Refractive Index: D20= 1.529 – 1.537 Maximum productivity rotary:D20 = -1o35 1

From the table above we can see , the main component of clove essential oil

is eugenol (76.8%), followed by −caryophyllene (17.4%), R-humulene (2.1%), eugenyl acetate (1.2%).9

4 Eugenol:

• Chemical formula:

Common name: eugenol Nomenclature name: 4- allyl-2methoxy-phenol hay 2- methoxy-4 (2 propenyl) - phenol

• Physical properties:

Colorless or pale yellow, liquid, transparent, darkened by exposure to air Has a characteristic smell of cloves

Solubility: Practically insoluble in water, soluble in 70% ethanol, insoluble in glycerol, miscible with ethanol 96%, with glacial acetic acid, with methylene chloride and with fatty oils

Molecular Mass: 164.20 g/mol Density: 1.06 g/cm3

Melting temperature: -9oC Boiling temperature: 256oC Refractive Index: 1.540 – 1.542 10

• Chemical properties:

Eugenol is an aromatic ring substance with a phenol functional group , containing a double bond and an ether

Evaluate the characteristic reaction of phenol: withFeCl3, with NaOH to form a phenolate salt

Take part in the characteristic reaction of an ether Join the addition reaction 1

CHAPTER 2: EUGENOL EXTRACT FROM CLOVE ESSENTIAL OIL

- Use organic solvents

Assemble a steam entrainment distiller as figure 3

Put about 5g of Clove buds in a 100ml flask Add 5 ml of water and some boiling ice Mark the water level to replenish the water lost during distillation and prevent the sample from drying out Heat the mixture until the distillation begins to stabilize Check the water level and add water as needed

When about 20 ml of distillate has been collected, stop heating and transfer the product to a 125 ml separatory funnel Rinse the flask with 5 ml of

CH2Cl2and add to the separating funnel Extract Eugenol with CH2Cl2 and collect the extract in a 25 ml erlenic flask Repeat the extraction with 5ml

CH2Cl2each time The dried extracts with Na2SO4 and smoke extract made anhydrous by pipette Evaporate the solvent to obtain pure eugenol.11

- Or extracting eugenol is based on the principle : Eugenol with OH of phenol when reacting with alkali will form alkaline eugenate This salt is soluble in water, insoluble in other components of the essential oil Based on this property, it is possible to separate alkaline eugenate from the unreacted essential oil Convert alkaline eugenate to eugenol by acid Purified by steam distillation or fractional distillation at reduced pressure

▪ Shake the essential oil with KOH Separate the potassium eugenate fraction Convert eugenate to eugenol with HCl solution Wash crude Eugenol with CaCO3 Purify by steam distillation.3

▪ Use 13-14% NaOH to convert eugenol to eugenate, separate the sodium eugenate Use HC1 to convert eugenate to eugenol Distill the fraction at reduced pressure of 18-20 mmHg, take the fraction with boiling point at138 - 140 °C 4

Figure 3: Steam entrainment distillation unit

▪ Use KOH to convert eugenol to eugenate The eugenate separation was carried out at 80 - 90°C Acidification with H2SO4 to convert eugenate to Eugenol Fractional distillation at 139°C yields pure eugenol 5

CHAPTER 3: SOME DERIVATIVES OF EUGENOL

1 Isoeugenol

Isoeugenol is rare in the composition of natural essential oils It has a milder fragrance than eugenol and is included in several fragrances Isoeugenol has a stronger antifungal effect than Eugenol.6

Isoeugenol is the starting material for the synthesis of several aromatic substances,

typically vanillin. 6

Isoeugenol is usually prepared by isomerization of eugenol in an alkaline medium at high temperature 11

Eugenol Isoeugenol

To explain the possible difference in biological activity and reactivity of Isoeugenol compared with that of eugenol, it is suggested that the transfer of the double bond closer

to the aromatic nucleus in the Isoeugenol molecule forms a conjugate chain, thereby affecting electron system in the benzene ring Nowadays, by quantum chemical method,

it is possible to calculate the charge distribution of atoms in the molecule, showing that the conversion of the allyl group to propenyl has clearly changed the charge distribution

at positions 3, 5 and 6 in the benzene ring 6

The commercial Isoeugenol product prepared from Eugenol consisting of a mixture of cis and trans forms has attracted much attention because the trans-Isoeugenol product has a milder aroma than cis-Isoeugenol and is used as a better flavoring agent 5

Trans isoeugenol Cis isoeugenol

Characteristics:

- Isoeugenol oily liquid is pale yellow, slightly fragrant than Eugenol5, odor

similar to carnations

- Density: 1,079 – 1,085 (g/cm3)

- Extract: 1,5720 – 1,5770

- Phenolic content: 99,5%

- Boiling point: 266oC

2 Zinc oxyde – Eugenol (ZOE):

For many years, the dental industry has used the complex between ZnO and Eugenol as a temporary filling material 12 ZnO can t Create complex with substances tamarind group t hoxy in ortho position compared with phenol OH:

With Eugenol, ZnO complexed according to the following equation:

In dentistry, ZOE is used in the simple way that ZnO powder is mixed with

Eugenol in a 1:1 ratio to form a homogeneous fine powder This fine powder used for temporary fillings is called Zinc Eugenat It is often used in dentistry when the decay is very deep or very close to the nerve or pulp chamber For persons with a dry socket as a complication of tooth extraction, packing the dry socket with a eugenol-zinc oxide paste on iodoform gauze is effective for reducing acute pain.13

The placement of a ZOE "temporary" for a few to several days prior to the

placement of the final filling can help to sedate the pulp But, ZOE had in vitro cytotoxicity majorly due to release of Zn ions.14 In spite of severe in vitro

cytotoxicity, ZOE showed relatively good biocompatiblity in animal study when ZOE was applied on dentin.15 When ZOE was used as dentin-protective based materials, use of dental composite resin on ZOE was strongly prevented due to its inhibition of resin polymerization through radical scavenging effect.16 It is

classified as an intermediate restorative material and has anaesthetic and

antibacterial properties The exact mechanism of anesthetic effect from ZOE was not revealed perfectly, but possibly through anti-inflammatory effect, modulating immune-cells to less inflamed status.17

3 Some eugenol derivatives have special properties

Dihydroeugenol

Substitute nitrogen at position 5 of

dihydroeugenol

Pain relief, no skin irritation 18

Sodium salt of dihydroeugenol Slight drop in blood pressure 18

Dihydroeugenol derivative with an amine

group attached to the 5 position

Cure bleeding but quite toxic 19

Esters of eugenol with carboxylic acids Significant pain relief 25

Axetyleugenol Axetyisoeugenol

Cosmetic flavoring , with the smell of

almonds 21

against drug-resistant Acinetobacter

baumannii 22

Methyleugenol Methyl isoeugenol

Anti-fungal, capable of repelling many

types of insects 23

pharmaceuticals 24

Table 2: Some eugenol derivatives have special properties