Objectives

Synthetic Aroma

To be acknowledged on general chemical

syntheses
To be informed on synthetic aroma
materials

Chemical combinations of floral fragrances

Contents
Introduction
Overview of organic synthesis
Typical reactions in synthetic fragrances
Synthetic aroma materials

Types

Lilac

Rose

Muguet

Phenyl ethyl
alcohol

30

35

15

20

25

Hydroxy
citronellal

30

45

Geraniol

2
4

48
2

20
5

2
45

4
1

5
1

5
3

4
4

5
5

40
-

10
60

3
4

Amyl
cinnamaldehyde
Benzyl acetate
Ionone

Jasmine Violet Carnation

Eugenol

55

Terpineol

25

Rose oil

The Production of Rose Oil

CH3

OH
H3C

CH3

CH3

O
H3C
H3C

CH3

CH3

CH3
CH3

H3C

CH3

Component
(-)-Citronellol
C14 - C16 Paraffins
Geraniol
Nerol
Phenethyl alcohol
Eugenol methyl ether
Eugenol
Farnesol
Linalool
(-)-Rose oxide
(-)-Carvone
Rose furan
beta-Damascenone
beta-Ionone

% of Oil
38
16
14
7
2.8
2.4
1.2
1.2
1.4
0.46
0.41
0.16
0.14
0.03

Threshold in Odor Units

-3
ppb
x 10
40
9500
75
1860
300
233
750
37
820
29
30
400
20
600
6
2300
0.5
9200
50
82
200
8
0.009
156000
0.007
42860

Rel. %
of odor
units
4.3
0.8
0.1
0.016
0.013
0.18
0.27
1
4.1
0.036
0.003
70
19.2

CH3

5
CH3

Nattaya Lourith, Ph.D.

Organic Synthesis

The Production of Rose Oil

Synthesis Aroma material

categorized by type of reaction

Overview of the
Organic Synthesis

- Substitution
- Addition
- Elimination
- Rearrangement
- Oxidation-Reduction (Redox)
9

10

Substitution

Addition

1. Nucleophilic addition

Alkyl halide SN1 and SN2

RX + OH- H2O
ROH + XSlow
SN1 : R:X
R+ +:X+
R + Nu
RNu or Fast
+
R + Nu
RNu+
SN2 : R:X + :NuRNu + :X- or
R:X + :Nu
RNu+:X-

SN2

Nattaya Lourith, Ph.D.

CH2 CH2 + Br2

+

C-------X

:Nu---C---X

CH2 CH2 + Br Br
CH2 CH2 + BrBr

CH2 CH2 + BrBr

CH2 CH2
Br
Br

2. Hydrogenation

CH3

SN1

CH2 CH2
Br
Br

11

RCH

CH2

+ H2

H 2 /P t

R C H 2 C H12 3

Elimination

Oxidation and Reduction

1. Cracking of petroleum hydrocarbon

H

Aldehydes are oxidized to carboxylic acids by a

variety of oxidizing agents, and it is possible to
do some selective reduction reactions

+ H2
H
2. Dehydrohalogenation

+ BX + X

B: +
3. Dehydration

-4

CH3OH

H C H

H C OH

O C O

-2

+2

+4

Oxidation

Reduction

+ H 2O
OH

13

Aliphatic compounds
-

CH4
-

Alcohols
Aldehydes
Ketones
Carboxylic acids
Esters

14

Alcohols
RX + OHRCH=CH2
RCHO
RX

15

Mg
Et2O

ROH + XB2H6

LiAlH4

RMgX

RCHX2
RCH2OH
RCOX

RCH(OH)2
Cr2O72H+

H2/Pd
BaSO4

RC CR

RCHO

RCH2OCrO2OH
-HX

RCHO
RCHO

R2CHOH
RMgX
RLi

17

Nattaya Lourith, Ph.D.

H3O+

RCH2OLi
RRCO

RRRCOMgX

R2CHAl(O-i-C3H7)2

RCH2OH
H3O+

i-C3H7OH

RRRCOH
R2CHOH

16

Ketones

-HOH

RCHXOH

RCH2CH2BH2H2O2/OH RCH2CH2OH

Al(O-i-C3H7)3

R2CO

Aldehydes
OH-

CO2

Hg2+
H2SO4
Cr2O72H+
CdCl2

RC(OH)2CH2R

-HOH

R2CHOCr2OH
RCOX

R2Cd

R2C(OLi)2

H3O+

R2C(OH)2

RCOCH2R
R2CO
RRCO
-HOH

R2CO
18

Esters

Carboxylic acids
RX
RX

CN-

Mg
Et2O

RCH2OH

H3O+

RCN

RCOOH

CO2

RMgX
MnO4-

RCOOMgX

RCOOH
H3O+

RCOOH

RCOOH

H+

RCOOR

ROH

RCOOR + HOH

H+
RO-

RCOOR + ROH

ROH

R2CO + HOOOCR

-RCOO-

RCOOR

19

20

Civetone
OC

(CH2)7COOMe
(CH2)7COOMe

H2/Pd-C

O (CH2)7COOMe
C
O (CH2)7COOMe

(CH2OH)2
HCl

O (CH2)7CH OH NaBH
4
O (CH2)7C=O

H3O+

Muscone
Br
Br

(CH2)11CHCN
(CH2)12CN Et NLi
2
H3C
H
H
CH2C=NH
CH2CN

(H2C)7
(H2C)7

21
Found in cis form in nature, used in perfumes as base note

H3C

(CH2)11CHCOOH
H
CH2C=O

WagnerMeerwein
Geraniol
cyclization

HOH

-HOH

OH

22

O
POCl3

Cl
Cl

OH-

Cl

Na/EtOH
0 oC

-terpene occurs in savin, coriander and cardamom oils

Lemon-like odor
Used in synthetic oils and technical products

(C6H5)3P=CH2

O
23
Diels-Alder addition and Wittig reaction

Nattaya Lourith, Ph.D.

(CH2)11CH2
H
CH2C=O

OH

OH

H3C

Terpinene

Limonene is found in most citrus oils. The (+) isomer is found in

orange, celery and caraway oils. The (-) isomer is found in pine
needle oils. Limonene is used in cosmetics and soaps.
OH

O+H2

H+

Used as a fixative and a modifier in

high-grade perfumes

Limonene

H3O+

H3O+

KOH

O=C

H3 C

PBr3

OH
OH

Na

24

Camphene
+

CHO

Geraniol

CHOAc

Rose odor used in perfumes, cosmetics and soaps

CHO

CHO

O3

Major component of rose, palmarosa, geranium and citronella oils

Ac2O

H2/Pd-C

NaNH2
CH3Cl

1. MeMgBr
2. H3O+

O
COOR
1. MeMgBr

Faint camphoraceous odor

+
CH2OH 2. H3O

Caproate

Nerol
1. LiAlH4
CHO 2. H+

Ester
Formate

Rose,
geranium
Geranium

Tiglate

27

Linalool
CHO

H2O2
OH-

CH2OH

Found in
neroli,
petitgrain,
bergamot
and
citronella

Organoleptic
Rose, orange

Acetate

Orange blossom, rose

n-Butyrate
i-Butyrate

Floral, leafy, orange

Formate

Rose, orange

i-Valerate

Herbaceous, sage

Rose, sweet
28

Esterification of linalool

CHO
O

OH
26

Rose,
lavender
Rose
Rose, apple
Rose

Propionate

OH
CH2OAc

25

Organoleptic
Rose leaf

n-Butyrate
i-Butyrate

1. LiAlH4
2. H+

OH-

OAc

Esterification of geraniol
Ester
Formate
Acetate

COOR

OH
Ac2O
CH2OH

CH2OAc

Used in technical products

COOR

Found in Siberian pine needle oil both in the (+)

and (-) isomers

(CH2OH)2

OH

N2H4

Found in (+) isomer in Bois de sol oil, (-) isomer in

Japanese Ho oil

Ester

Organoleptic

Formate
Acetate
Propionate

Citrus, herbal
Floral, fruity
Bergamot, peach

n-Butyrate
i-Butyrate
i-Valerate

Bergamot, fruity
Lavender
Fruity, apple

Used in perfumes, cosmetics and soaps

Prepared by the epoxidation of geranial followed by
the Wharton reaction

Nattaya Lourith, Ph.D.

29

30

Citronellol
HO
O 1. Zn/BrCH COOEt
2
2. H3O

COOEt

OH

COOEt

PTSA

LiAlH4

Esterification of citronellol

Li
NH2(CH2)2NH2

OH

Found (+)-citronellol in Java citronella oil and (-) isomer in

Reunion geranium oil

Ester

Organoleptic

Formate

Peach, plum, rose

Acetate

Citrus, rose

Propionate

Fruity, rose

n-Butyrate

Fruity, rose

i-Butyrate

Fruity, rose

Valerate

Honey, herbaceous

Caproate

Rose

Tiglate

Fruity, rose

Rose-like odor, used in perfumes, cosmetics and synthetic

31
rose compositions

Menthol
OH

H
H

H OH
+ menthol

+ isomenthol

Powerful odor with

cooling effect used in
dental products,
chewing gums and
cigarettes

Esterification of menthol
H

OH

32

H H

OH

+ neomenthol + isoneomenthol

Ester
Acetate
i-Valerate
Lactate

H2/Ni

OH

Prepared by
reduction of pulegone

33

34

Citronellal
600 oC

HCl

OH-

Cl

MnO2

Hydroxycitronellal
CHO

OH

H2
Pd-C

CHO
CHO

OH H2SO4
SO3H

OH NaHCO3
SO3H

CHO

HO

A lily of the valley odor

Used as a base note in lilac and mouget
combinations

Colorless liquid
Used in perfumes, cosmetics and soaps
Prepared from -pinene thermal rearrangement
and 1,4-addition of HCl

NaHSO3

HO

Found (+)-citronellal in rose, lemon and citronella

oils, (-) isomer in Java lemon oil

Nattaya Lourith, Ph.D.

Organoleptic
Berry, minty, woody
Fruity, woody
Citrus

35

36

Citral
O

Br
+

Carvone

H EtO-

EtOOC

EtOC C

OH

H2
Pd-BaSO4

H3O+

NOCl

1. BrMgC=COEt
2. H3O+

COOEt
EtOC=C

OH

OH

(-)-Carvone has mint odor, used in dental

products

Found mainly in lemongrass

Used in perfumes, cosmetics and soaps

Prepared from -terpineol

37

Menthone
H2
Pd-C

H3O+

Li/NH3

OMe

OMe

Found (+)-piperitone in Japanese mint oil and (-)

isomer in eucalyptus oil

peppermints oils

A camphoraceous odor, used in technical products

and for the synthesis of menthol

A peppermint odor with less cooling effect

than menthol
Used to compound synthetic oils

Prepared via Birch reaction

39

COOEt
1. H+
2. CrO3

40

Fenchone

Pulegone

OAc

38

Piperitone

Found in pennyroyal and

Ac2O
CHO OAc-

O
H+

(+)-Carvone has caraway odor, used in dental

and oral preparations

Pale yellow liquid, Strong lemon-like odor

EtNH(CH2)2COMe
EtO-

NOH

Found (+)-carvone in caraway and dill seed oils,

(-) isomer in spearmint oil and racemate in
gingergrass oil

A mixture of neral and geranial

NOH

EtO-

OH

CHO

+
CHO

Cl

OH

i-pulegone

COOEt

Zn
BrCH2COOEt

Ba(OH)2

O
pulegone

HO

O
COOH

Pb

COOEt

PBr3

COOEt

COOEt
O

CH3I
Na

H2/Pt

COOH

Found in lemongrass oil

Found in fennel seed oil, has a camphoraceous odor

Isopulegone is found in pennyroyal

Imparts a pine tone to room sprays and bath preparations

Pulegone is used in soaps and dental products 41

Prepared via a Reformatsky reaction and a Ruczicka

cyclization

Nattaya Lourith, Ph.D.

42

Benzyl alcohol

Phenylethanol

Found free in tuberosa, jasmine, hyacinth

and ylang-ylang oil
- Faint odor, used in perfumes, cosmetics and
soap
- Used in floral oils such as tuberosa, jasmine,
gardenia and ylang-ylang

Found free in neroli, geranium and rose oils

Found as benzoate or phenylacetate in
neroli bigarade and rose oils

OH

CHO
+ HCHO

OH-

43

- Used in perfumes, cosmetics and soaps

Odor

Found as cinnamate ester in oils, balsams

Honey, fruity, rose

Propionate

Rose, balsamic

n-Butyrate
i-Butyrate
i-Valerate

Floral, grape

and resin such as styrax and Peru balsam

Free alcohol has hyacinth odor

Fruity, rose

Used in lily, lilac and hyacinth perfumes

Fruity, rose
Ester

Odor

Hexanoate

Fruity, green, rose

Octanoate

Green, fruity, floral

Benzoate

Honey, rose

+ CH3CHO

Anthraniline Fruity, floral

Cinnamate

Balsamic

45

Esterification of Cinnamyl alcohol

Ester
Formate

Organoleptic
Green, balsamic

Acetate
Propionate
n-Butyrate

Floral, balsamic
Fruity, spicy, balsamic
Fruity, balsamic

i-Butyrate
i-Valerate

Fruity, balsamic
Fruity

CHO

OH-

OH

LiAlH4

Aldol condensation then hydride reduction46

Benzoic acid
Found in anise seed, cinnamon leaves and cloves
White solid used for ester preparation
Widely used as preservative

47

Nattaya Lourith, Ph.D.

44

Cinnamyl alcohol

Esterification of Phenylethanol
Ester

Friedel-Crafts reaction
with ethylene oxide

- A honey-rose odor alcohol

+ HCOOH

Prepare by cross Cannizaro reaction

Acetate

OH

HCl/AlCl3

- Used as fixative

Carbonation of
Grignard
compound then
acid hydrolysis

MgBr

COOMgBr
CO2

COOH

H+
48

Salicylic acid

Cinnamic acid

Found in anise, cassia, pennyroyal and ylang-ylang oils

White solid used for ester preparation

Found in styrax oil, cassia and basil

Used as a preservative

White solid used for ester preparation

OH
Prepare via Kolbe
synthesis

OH
COOH

1. CO2/OH
2. H+

CHO
+ BrCH2COOEt Zn

COOEt

COOH

H+

Prepare via Reformatsky reaction

49

50

Esterification of Phenylacetic acid

Phenylacetic acid

Ester

Organoleptic

Found free and in ester derivative in Japanese

mint neroli bigarade oils

Methyl

Sweet, floral and honey-like odor

Honey, sweet,
jasmine

Ethyl

Honey, sweet

Used in perfumes and soaps

Propyl

Honey, apricot, rose

i-Propyl Honey, wine, rose

Allyl

Honey, sweet
Ester

CH2Cl

CN-

CH2CN

H+

CH2COOH

51

Anthranilic acid

NH

Br2/OH-

NH2
COO-

H+

Honey, rose

i-Butyl

Honey, musky

Hexyl

Rose, green, wine

Methoxy

Woody, musty, green

i-Eugenyl

Honey, clove, floral

52

Esterification of Anthranilic acid

Found as methyl ester in neroli bigarade oil

and jasmine, tuberosa, gardenia flower oils
and orange, mandarin and bergamot leaves
O

Organoleptic

Butyl

Ester

NH2
COOH

Organoleptic

Methyl
Ethyl
Butyl

Orange blossom
Fruity, grape, floral
Mild, sweet, plum

Linalyl
Phenethyl

Orange, floral
Fruity, floral, iris

Prepare via Hofmann rearrangement of

phthalimide in 85% yield
53

Nattaya Lourith, Ph.D.

54

Anisaldehyde

Benzaldehyde

Found from anise and fennel oils

Found as glucoside amygdalin in cinnamon bark
and leaf oils and almond and apricot oils

Odor of blooming hawthorn

Used in perfumes and soaps

Powerful crush bitter almond when free

Used in lilac, mimosa, heliotrope and sweet pea blends

Used in cosmetics and soaps

CHO

CH3 1. CrO Cl
2 2

Prepare via
55
oxidation reaction

2. HOH

Prepare by
Williamson
methylation
of cresol and
oxidation with
manganese
dioxide

Vanillin

Me

Me
Me2SO4/OH-

OH

CHO
MnO2
56

OMe

OMe

Phenelacetaldehyde

Found in vanilla bean

Not found in nature

Strong odor of vanilla

Odor of hyacinth

Used to impart a sweet and lasting note to floral

and fancy perfumes

Used in perfumes, cosmetics and in hyacinth, jonquil,

narcissus, jasmine and lilac blends

CH=N+H2
HCN/HCl

OMe
OH

Provide top note in floral

CHO
HOH

OMe

OMe

OH

OH

Prepare by Gattermann reaction

57

Prepare by
chromic acid
oxidation of
phenylethanol

Cinnamaldehyde

OH

Organoleptic

Cinnamon

Odor of cinnamon used in perfumes

CH3

Cinnamon, coumarin, spicy

C3H7

Spicy, amber

C4H9

Green leaf

C5H11

Jasmine, lily

C6H13

Jasmine

C7H15

Leafy

C2H5

+ RCH2CHO

OH

Nattaya Lourith, Ph.D.

CHO

Prepare via Aldol condensation

58

Cinnamaldehyde derivatives

Found in cassia leaf and bark and cinnamon bark oil

CHO

CHO

H2CrO4

R
59

Spicy

CHO
R

60

Cyclamenaldehyde

Acetophenone

Not found in nature

Obtained from Stirlingia latifolia oil

Odor of floral-green with cucumber-melon

Strong sweet and aromatic odor

Used in floral such as lily, lilac, peony and magmolia

Used in floral such as lilac, hawthorn and wisteria

Used in soaps

Me
Me
CH=CCHO CH2CHCHO

CHO
EtCHO
OH-

H2
protect
carbonyl

R
(MeCO)2O
AlCl3

Prepare via
Aldol
condensation
61

Prepare via FriedelCraft reaction

COMe

62

Carvacrol

Thymol
Found in thyme and ajowan oils

Found in majoram, origanum, savory and thyme oils

White solid with thyme odor

Prepare by hydrogenation reaction followed by Se
dehydrogenation

Used in soaps and dental products

Prepare via Sulfonation reaction

H2/Pt

OH

Se
heat

SO3H

SO3
H2SO4

OH

OHheat

OH

63

64

Anethole

Eugenol

Obtained from anise and funnel seeds

Found in free and glucoside forms in cloves oil

White solid with sweet odor

Pale yellow liquid with strong odor

Used in dental products

Used in perfumes, soaps and cosmetics

Prepare via haloalkylation reaction

OMe

OMe
CH3CH2CHO
HCl/ZnCl2

OH

OH-

OMe CH2=CHCH2Br
OH

CHClCH2CH3

Nattaya Lourith, Ph.D.

Prepare via Claisen rearrangement

OMe

65
CH=CHCH
3

OCH2CH=CH2
OMe
heat

OH
OMe
66

CH2CH=CH2

Methyleugenol

Isoeugenol
Obtained from nutmeg and ylang-ylang oils

Obtained from citronella oil from acacia flowers

Pleasant odor

Softer odor then eugenol

Used in floral bouquets and base of

carnation scents

Used in perfume combination of carnation and

oriental as a modifier

OH
OH

OH
OMe

1. OH2. H+

OMe
CH=CHCH3

CH2CH=CH2

Prepare via
Isomerization
reaction
67

OMe

MeI/OH-

OMe
OMe
CH=CHCH3

CH2CH=CH2

Prepare by
Williamson
methylation
of eugenol 68

Blackcurrant

Fruity
Anapear

Etaspirene
Neocaspirene

R1 R2 R3 R4 R5
Et H H Me Me
H Me H H iPr

A fruity-green pear note

Exp. Emporio Armani Elle (G. Armani, 1998)
69

Galbanum

Etaspirene Exp. Pleasures (E. Lauder, 1995)

Neocaspirene Exp. Le monde est beau (Kenzo, 1997)
70

The green of leaves

Glycolierral

A fruity, pineappletype note in

Fougre
Exp. Cool water
(Davidoff, 1988),
Egoste Platinum
(Chanel, 1993)

CHO

HO(CH2)2OH
H
-Dynascone

-Dynascone
71

Nattaya Lourith, Ph.D.

An ivy-leaf odor
Exp. Jadore (C. Dior, 1999)

72

The green of leaves

Sea-breeze

Undecavertol

Calone 1951

A marine note

A violet-leaf odor
Exp. Extravagance dAmarige (Givenchy, 1998),
Sunwater (Lancaster, 1997), Escape for Men
(C. Klein, 1993)
73

Watermelon

Rose

Melonal

Doremox and Phenoxanol or Mefrosol

Exp. Birmane (Van Cleef & Arpels,

1999), Bvlgari E.D.P. (Bulgari, 1994)

A watermelon note
Exp. Allure (Chanel, 1996)

75

Jasmine & Magnolia

76

Woody

Hedione and Magnolione

Firsantal : a woody-sandal-floral note

Exp. Coriandre (Couturier,

1973), Eden (Cacharel, 1994)
77

Nattaya Lourith, Ph.D.

Exp. New West for her (Aramis, 1990), Escape for her
(C. Klein, 1991), L Eau dIssey (I. Miyake, 1992), LEau
dEden (Chcharel, 1996), Cool Water fem (Davidoff,
74
1996), Polo Sport Woman (R. Lauren, 1996)

Exp. Ultra Violet (P.Rabanne, 1990)

Firsantol : a woody-aromatic-musky note
Exp. 212 foe men (C. Herrera, 1999)

78

Ambery

Woody
Iso E Super

Spirambrene

Exp. Fahrenheit (C.Dior, 1988), Trsor (Lancme,

1991), Fminit du Bois (Shiseido, 1992),
Dclaration (Cartier, 1998)
79

References
1. Arctander S. Perfume and Flavor Chemicals
(Aroma Chemicals). V. 1. Illinois: Allured; 1994.
2. Gimelli SP. Aroma Science. New York: Micelle
Press; 2001.
3. Kraft P, Bajgrowicz JA, Denis C, Frter G. Odds
and trends: recent developments in the
chemistry of odorants. Angrew. Chem. Int. Ed.
39:2980-3010, 2000.
4. Nattaya L. Synthetic Aroma material in
Aromatic Science 1701351 [Lecture handout].
Chiang Rai: MFU;2007-2010.
81

Nattaya Lourith, Ph.D.

A floral-oriental odor
Exp. Kenzo pour Homme (Kenzo, 1991)

80

Thank you
for your
attention
82