Simple Inexpensive & Safe Method of Preparation of Eugenol Derivatives and Caryophyllene Oxide at Room Temperature

without any coolant

Benjamin Lukas

Clove OilClove oil is an essential oil extracted from clove plant, Syzygium Aromaticum. It isoften found sold at health food store. It is produced by steam distillation.There are 3 types of this essential oil of clove: Bud oil: the most expensive type derived from flower-bud of S. Aromaticum Stem oil: derived from twigs of S. aromaticum Leaf oil: the least expensive type derived from leaves of S. Aromaticum

Main Components of Clove oil:• Eugenol (up to 80%)• Caryophyllene (up to 16%)

And other Minor Componentsconsisting of 20 chemicalsIncluding:• Isoeugenol• Methyl eugenol• Methyl isoeugenol• Eugenyl acetate• Isoeugenyl acetate and others

Production of Clove Oil

Material Steam Steam generator

Essential oil Extraction machine Plant extract

Chiller Condensor Distillate Oil water separator Essential oil

Steam Distillation Unit for Local Farmers in Indonesia

Uses of Clove Oil

Clove oil is used as analgesic and others such as:• Home remedy for relieving toothache• Ingredience of cat spray deterence• Flavoring agent for some medicine• Anaesthetic for fish• To extract eugenol and caryophyllene from which other

derivatives of eugenol and caryophyllene are synthetically made.

1st Main Components of Clove Oil: Eugenol

• Eugenol, 4-allyl 2-methoxyphenol is the main component of clove oil, a derivative of a phenylpropene with a methoxy group at meta position and hydroxy at para position.

• It is a pale yellow clear liguid present in clove, nutmeg, cinnamon, cinnamomum tamala, bay laurel , sweet basil, African basil, Holy basil, dill, Japanese star anise, lemon balm, vanilla, celery and pimenta racemosa

• When it is freshly produced the colour is dark brown, after purification it becomes pale yellow but readily turn brown on exposed to the air.

• It is soluble in most organic solvents, but almost insoluble in water.• It has strong , clove-like smell and spicy with pungent taste.

Extraction of Eugenol

• Crude eugenol can be extracted very easily from crude clove oil by using its polar character and the non-polarity of the rest of the components of clove oil. The water used in this process can reused several times until it is saturated with the side product. Local farmers in Indonesia have been taught the method of this extraction so that it has added value on their original product of clove oil. The purity of this crude eugenol obtained using this method is about 95%.

• Further purification of crude eugenol can be achieved by simple distillation to give 99% purity . When freshly prepared it is pale yellow clear liquid which quickly turns yellowish to finally brownish when exposed to air

• Details of this simple industrial process can be obtained on request.

Uses of Eugenol

• Eugenol is mainly used as antiseptic, analgesic, perfumery and as flavoring agent.• As flavoring agent, it is used in non-alcoholic beverages, candy, baked goods,

puddings, ice creams, ices, chewing gums, condiments and meats.• Eugenol when combimed with zinc oxide has been used in dentistry for many years

as root canal sealing.• It is also used as wood preservative.• Eugenol and some of its derivatives can be used as valuable thermal stabilizers and

antioxidant for plastics made from starch of tapioca or corn etc (bioplastics) for packaging film when coated with certain compounds such as chitosan or cyclodextrin.

• Eugenol is a key ingredient in Indonesian kretek cigarette

Uses of Eugenol

Derivatives of Eugenol• Clove oil can be extracted from either leaves, stem or buds of clove tree• The main component of clove oil is eugenol which can be extracted by

simple chemical reaction making use of its polarity character to give min 95 % purity. Further simple vacuum distillation will give eugenol of 99% purity.

Derivatives of eugenol produced by industry:• Isoeugenol Hydroeugenol• Eugenol acetate Isoeugenol acetate • Methyl eugenol Methyl isoeugenol

Price of Eugenol & Caryophyllene & Derivatives

Vigon International, East Stroudberg, PA, USANo Compound Price 1kg 1 kg (5kg

purchase)1 kg (10kg purchase)

1 kg (50kg purchase)

1 kg (200kg purchase)

1 Minyak cengkeh (Clove leaf oil)

2 Eugenol $117 $52 $38 $36 $32

3 Isoeugenol $170 $80 $60 $56 $50

4 Eugenyl acetate $185 $95 $75 $71 $65

5 Isoeugenyl acetate $184 $94 $74 $70$

6 Methyl eugenol $150 $85 $72 $69 $65

7 Methyl isoeugenol $190 $100 $80 $76 $70

8 Benzyl eugenol $611 $521 $501

9 Dihydroeugenol $147 $82 $68 $66 $62

10 Caryophyllene

11 Caryophyllene oxide

12 Caryophyllene acetate $147 $82 $68 $66 $62

13 Caryophyllene formate

• Clove Leaf Oil is the raw material used for synthesis of the above compounds U$12 – U$15/Kg (Indonesian companies such as Indesso Aroma, Djasula Wangi, Nusaroma)

Isoeugenol

• Isoeugenol is an isomer of eugenol• It has a characteristic floral odor reminiscent of carnation.• It exist as 2 isomers as cis and trans isoeugenol• Only trans-isoeugenol is valuable, it has softer aroma than eugenol and therefore used as carnation note

in fragrance.• As flavoring agent it is used in non-alcoholic beverages, candy, condiments, chewing gums, ice creams

and ices.• Isoeugenol is produced commercially by isomerization process but the proses produces min 7% tarry

side product with the catalyst used losing some of its catalytic power.• There are 2 types of catalysts used for isomerization of eugenol, both are like secret to most industry .

One of the catalysts is an expensive Ru/Rh organometallic compounds while the other is a very cheap one.

• Because of the difference of boiling point of the isomers trans and is only by 5C, the separation of the isomers is only possible by fractional distillation. Details of the process with conversion greater than 99% conversion can be obtained on request.

Isomers of Isoeugenol

Trans-Isoeugenol cis-Isoeugenol

Fractional distillation in Lab

Fractional Distillation in Industry

Methyl Eugenol• Methyl eugenol is a colorless or pale yellow clear liquid with a bitter taste and clove-

carnation aroma. It is an ether compound of eugenol with the bpt of 244 C but evaporates readily at room temperature

• It darkens and slowly thickened when exposed to air• It is presence in some herbs and spices such as lemon grass, basil, mace, tarragon,

bay leaf, nutmeg, allspice and clove. In fruits it is found in banana, grapefruit.• It has delicate clove-carnation odor with a bitter burning taste.• As flavoring agent, it is used in non-alcoholic beverages, candy, baked goods, jellies ,

ice creams and ices.• It is produced using methylation process with dimethylsulfate (DMS) as methylating

agent under certain condition as DMS is very toxic compound. • Details of industrial process can be obtained on request.

Uses of Methyl Eugenol

Methyl eugenol is used as:• Flavoring agent in various food and non-beverage drinks such

as in jellies, chewing gum, baked food, candy, pudding, relishes and ice cream.

• As fragrance in perfumery, toiletries creams and lotions, soaps and detergents.

• As insect attractant for fruit flies etc.

Methyl Isoeugenol

• Methyl isoeugenol is a methyl ether compound of isoeugenol, a colorless or pale yellow clear liquid with a bpt of 262-264 C found in some essential oils. It occurs in both isomers cis and trans but only the trans isomer is valuable.

• It has a delicate clove-carnation odor with burning bitter taste.• It is used in flavor and fragrance formulations• As flavoring agent, it is used in non-alcoholic beverages, candy, baked goods, gelatins,

puddings, chewing gums and ice creams ices.• Is is also used as anxiolytic and antidepressant• In industry it is prepared by first converting eugenol to trans-isoeugenol and then

methylating this product to become trans- methyl isoeugenol. • Purification then produce pure trans methyl isoeugenol. Separation of trans from cis can be done at the end of the process.• Details of the process with yield greater than 95% can be obtained on request.

Isomers of Methyl Isoeugenol

trans-methyl isoeugenol cis-methyl isoeugenol

Eugenol Acetate

• Eugenol acetate is a white solid with mpt of 26 C and bpt 281-285 C. . It is soluble in most organic solvents and essential oils. It has characteristic odor reminiscent of clove oil with burning aromatic flavor• It is used as flavor and fragrance agents• As flavoring agent it is used in non-alcoholic beverages, candy, ice creams, baked goods, cheing gums, condiments and meats.• It is prepared by esterification of eugenol in the presence of a catalyst.

Eugenol + acetylating agent catalyst Eugenol acetate + acetic acid

• Details of the process can be obtained on request.

Isoeugenol Acetate

• It is 2-methoxy-4-propenylphenyl acetate, a white crystal with a mild aroma resemblance of rose-carnation with mpt of 79C and bpt of 283C.

• It is used as floral flavor and fragrance. It is also used in fixed scent fragrance of carnation flavor combined with vanillin.

• As flavoring agent, it is used in non-alcoholic beverages, ice creams, ices, baked goods and chewing gums.

• It is produced by refluxing isoeugenol with acetylating agent and after exclusion of acetic acid, crystals of isoeugenol acetate is obtained. Further purification affords pure compound.

• The above preparation produce yield less than 20%, but if a certain catalyst is added to the reaction more than 90% yield is obtained.

• Details of process with yield greater than 90%can be obtained on request.

Dihyydroeugenol

• It is eugenol with the propylene group has been fully hydrogenated. It is a liquid with an aroma of clove, sharp, spicy, sweet similar to eugenol.

• In perfume it is a great addition to jasmin, carnation or spicy flower accords.• It is prepared by reacting eugenol with hydrogen in the present of a catalyst

at room temperature for several hours.

• Eugenol + H2 catalyst Dihydroeugenol

• Dihydroeugenol obtained is then purified by simple distillation

2nd Main Components of Clove Oil:Caryophyllene

• Caryophyllene is a sesquiterpene found in many essential oils such as oil of clove, cinnamomum tamala, basil, rosemarry, oregano, cannabis, hop, black caraway, true cinnamon and black pepper . Its presence in black pepper contributes to its spicyness.

• It is usually found in a mixture with isocaryophyllene and alpha caryophyllene

• It has terpene odor between that of clove and turpentine• It has bpt of 254 C and soluble in alcohol but insoluble in water.• As flavoring agent, it is used in chewing gums, candy, baked goods, ice

creams, ices, non-alcoholic beverages and condiments

Caryophyllene Derivatives

• After eugenol is extracted from clove oil, beta caryophyllene can be purified using fractional distillation from 20 other components. The industrial beta caryophyllene has purity of about 85%.

• Derivatives of beta caryophyllene produced by industry: - Caryophyllene oxide - Caryophyllene acetate - Caryophyllene formate - Caryophyllene alcohol

Caryophyllene Oxide

Caryophyllene oxide is widely used in industry as a flavour and fragrance compound and recently has been patented as antitumor agent. It is an oxygenated form of the sesquiterpene which exists as white crystalline solid with a melting point of 62 C. There is no known method of preparation of this compound in the literature as the method is kept secret by the manufacturers.It is only known that the raw material used for production of caryophyllene oxide in industry is beta caryophyllene derived from the clove oil.

Production of Caryophyllene Oxide

CLOVE LEAF/BUD/STEM

CLOVE OIL

EUGENOL CARYOPHYLLENE

CARYOPHYLLENE OXIDE

Preparation of Caryophyllene Oxide

In this work caryophyllene oxide was prepared by reacting caryophyllene (86% purity)withpercarboxylic acid prepared in situ using carboxylic acid and H2O2 . A catalyst isneeded for the preparation of caryophyllene oxide at room temperature withoutneeding any coolant. The yield is less than 90% RCOOH + H2O2 RCOOOH + H2O

Preparation of Caryophyllene Oxide

Variables used in the reaction:Stoichiometry, reaction time and the type and amount of the catalyst used. If the conditions are not followed then the the temperature will rise up very quickly.Details of the process can be obtained on request.

Caryophyllene + RCOOOH catalyst, RT Caryophyllene Oxide + RCOOH

Price of Caryophyllene Oxide

Caryophyllene oxide is very much more expensive than caryophyllene itself or any other eugenol derivatives because of the difficulty in producing it.

Just for comparison the price at Sigma-Aldrich for 1 gram caryophyllene oxide of 99 % purity is $70.00 compared to the price of caryophyllene which is $ 3.00 per 1 kilogram. The price of the most expensive of eugenol derivatives is only over $501.00 per kilogram.

The cost of chemicals used for preparation of 1 kg caryophyllene oxide is less than $1Clove leaf oil, eugenol and caryophyllene (86% purity) can be obtained easily from Djasula Wangi, Indesso Aroma and Nusaroma in Indonesia.

GCMS of Caryophyllene Oxide

Caryophyllene obtained is 99% pure as indicated by GC MS analysis.

References

References:

- Chemistry of Natural Compounds 23, 393, 1987 The Chemistry of caryophyllene and related compounds by A.V.Tkachev- CA Patent 2440534- US Patent 4229599- US Patent 3978089- Journal of Natural Products, 575 999, 1992

Thank you………………

For consultation of this project and others previously reported please contact :

benjaminlukas@yahoo.com