Spices
Linalool is a kind of terpene alcohols and is one kind of famous perfume compounds. It is the mixture of two isomers (α-linalool and β-linalool). It is extracted from camphor oil (from camphor tree) or synthesized from the α-pinene or β-pinene contained in turpentine. It is colorless oily liquid with sweet and tender fresh flowers and a fragrance of Convallaria majalis. It is easily soluble in organic solvents such as ethanol, ethylene glycol and diethyl ether but insoluble in water and glycerol. It is easily subject to isomerization and is relatively stable in alkali. It has a density (25 ℃) of 0.860~0.867, the refractive index (20 ℃) of 1.4610~1.4640, optical rotation (20 ℃) of -12 ° ~-18 °, the boiling point being 197~199 ℃, and the flash point (open ended) of 78 ℃. Linalool with alcohol content higher than 95% is an important spices for floral fragrance used for perfumes, soaps and other fragrance industry. It is also widely used in flowers oils of lending lily, lilac, sweet pea, and orange blossom as well as the compound perfume of amber incense, oriental fragrance, and aldehyde-type fragrance, cosmetics perfumes and food flavor. It can also be used as the spices of lemon, lime, orange, grape, apricot, pineapple, plum, peach, cardamom, cocoa, and chocolate. Drug containing 92.5% alcohol content is used as the raw material drugs in the pharmaceutical industry for producing isophytol which is an important intermediate in the preparation of vitamin E. It can also be used as raw material for producing valuable spices linalyl acetate and some other esters. Linalool belongs to open chain terpene tertiary alcohol. It has two double bonds. However, it contains an asymmetric carbon atom, so it has three kinds of optical isomers. In Nature, all three kinds of isomers are present with the amount of I-body being the highest, accounting for 70% to 80% of the total amount of the three. I-body is mostly presented in linalool oil (containing about 80 to 90%), champa, lavender oil, lime oil, neroli oil, clary sage oil, aloeswood oil, lemon oil, rose oil, cananga orodrata oil and some other kinds of essential oil; its d-body is mostly presented in coriander oil (containing about 60% to 70%), sweet orange oil, nutmeg oil, palmarosa oil and other kinds of essential oil; its dl-form is mainly presented in the essential oils of clary sage and jasmine. All the three kinds are transparent colorless oily liquid with lilies and citrus-like fragrance. In addition, because of the close distance between its hydroxy group and allyl group, its chemical nature is very influential. In the presence of sodium metal in ethanol solution, it can be easily be reduced to generate dihydro-myrcene; in the presence of a platinum catalyst or Raney nickel catalyst, it can be reduced to the tetrahydro linalool to become saturated alcohol. Owing that it is a kind of tertiary alcohol, in strongly acidic medium, it can subject to isomerization; in dilute acid medium, it undergoes dehydration to become esters. It is stable in alkaline medium. The LD50 of oral administration for Rat is 2790 mg /kg.
Lavender
Linalool is the major antimicrobial ingredient of lavender essential oils. It can inhibit the growth of 17 bacteria (including Gram-positive and Gram-negative bacteria) and 10 fungi. In vitro experiments show that the narrow-leaf lavender essential oils, at concentrations below 1%, can inhibit the newly penicillin I resistant Staphylococcus aureus and Enterococcus faecalis.
Content Analysis
Take 10 mL of sodium sulfate pre-dried sample and put it into a 125 mL of glass-stoppered Erlenmeyer flask pre-cooled by an ice bath. Add 20 mL of dimethylaniline (toluidine product) in cold oil and mix thoroughly. Add 8 mL of acetyl chloride and 5 mL of acetic anhydride, cool for several minutes, then place at room temperature for 30min, then immerse the flask in a water bath and maintained for 16h at 40 °C ± 1 °C; Apply ice-water for washing acetyl oil for three times with 75 mL each time. Then repeatedly wash with 25 mL of 5% sulfuric acid solution until the separated acid layer no longer exhibiting cloudy-like or doesn’t have further dimethylaniline odor coming out so that dimethylaniline was further removed. First apply 10 mL of 10% sodium carbonate solution for washing acetylated oil, followed by successive washing with water until washing to being neutral to litmus. After complete drying with anhydrous sodium sulfate, accurately weigh the acetylation oil of about 1.2g, and then measure it according to the "ester assay" (OT-18). Linalool (C10H18O) content (L) is calculated as follows;
L = 7.707 (b-s) /W=0.021 (b-s)
Where L--linalool content, %;
b-the consumed volume of 0.5 mol/L of hydrochloric acid in blank test, Mi;
s--the consumed volume of 0.5 mol/L of hydrochloric acid for titration of the sample solution, ml;
IV-sample sample, g.
Method II, measure the amount using non-polar column protocol based on the Gas Chromatography Method (GT-10-4).
The above information is edited by the chemicalbook of Dai Xiongfeng.
Toxicity
Adl 0~0.5 mg/kg (FAO/WHO.1994).
GRAS (FDA, §182.60, 2000).
LD50 2790 (rat, oral administration).
Limited use
FEMA (mg/kg): Soft drinks 2.0; cold drink 3.6; candy 8.4; Bakery 9.6; pudding Class 2.3; gum 0.80 to 90; meat 40.
Chemical Properties
It is colorless liquid with fragrance similar with bergamot. It is insoluble in water, but miscible with ethanol and ether.
Uses
1. It is used for the preparation of cosmetics, soaps, detergents, food and other flavors.
2. GB 276011996 states it is classified into food flavor allowed for temporary use. It is mainly used for the preparation of flavors or aromatic seasoning of pineapple, peach, and chocolate.
3. It is widely presented in flowers, fruits, stems, leaves, roots and green Rosa Chinensis viridiflora. It has a wide range of application, not only for all the floral flavors, such as sweet bean curd, jasmine, Convallaria majalis, lilac, etc., it can also be applied in fruit flavor type, Fen-flavor type, wood flavor type, aldehyde flavor type, oriental flavor type, amber scent type, chypre type, fern-type and other non-flower type of flavor. It can also be used in formulating orange leaf, bergamot, lavender, and some kinds of artificial oils such as hybrid lavender oil. It is mostly used in soap or flavor. It can be used for food flavor.
4. Linalool is a kind of important spices and is the blending raw materials for producing various kinds of artificial oil, also used extensively for the manufacturing of various esters of linalool. Linalool has an important position in the ester-type perfumes and other cosmetic formulations. Linalool can generate citral through oxidation and can also be used for the synthesis of many other kinds of spices.
Production method
1. The commercial linalool is mainly isolated from natural essential oils including aloeswood oil, rosewood oil, coriander oil, and linalyl oil. Using efficient distillation column for fractionation can produce crude product of linalool with secondary fractionation obtaining finished product with a content being higher than 90%. Synthetic linalool can use β-pinene as raw material with pyrolysis yielding myrcene. Treatment with hydrogen chloride generates a mixture comprising linalyl chloride. Linalyl chloride can have reaction with potassium hydroxide (or potassium carbonate) to generate linalool.
2. It is existed in free form in camphor oil: using acetyl boric anhydride converting the linalool contained in camphor oil into acidic borate ester, and then through distillation, re-crystallization, and saponification to obtain the finished product.
3. Use 6-methyl-5-hept-ene-2-ketone to have condensation reaction with sodium acetylide to obtain dehydrolinalool, further undergoing reduction reaction at wet ether solution with metal sodium to obtain the linalool.
Description
Linalool has a typical floral odor free from camphoraceous and
terpenic notes.1 Synthetic linalool exhibits a cleaner and fresher
note than the natural product. It can be prepared synthetically
starting from myrcene or from dehydrolinalool.
The optically active forms (d- and ι-) and the optically inactive
form occur naturally in more than 2 0 0 oils from herbs, leaves,
flowers, and wood; the ι-form is present in the largest amounts
(80 - 85%) in the distillates from leaves of Cinnamomum cam phora var. orientalis and Cinnamomum camphora var. occidentalis
and in the distillate from Cajenne rosewood; it also has been
reported in: champaca, ylang-ylang, neroli, Mexican linaloe, ber gamot, lavandin, and others; a mixture of d- and ι-linalool has
been reported in Brazil rosewood (85%); the d-form has been
found in palmarosa, mace, sweet orange-flower distillate, petit grain, coriander (60 - 70%), marjoram, Orthodon linalooliferum
(80%), and others; the inactive form has been reported in clary
sage, jasmine, and Nectandra elaiophora.
Chemical Properties
liquid
Chemical Properties
Linalool has a typical pleasant floral odor, free from camphoraceous and terpenic notes. Synthetic linalool exhibits a
cleaner and fresher note than the natural products.
Chemical Properties
Linalool occurs as one of its
enantiomers in many essential oils, where it is often the main component. (3R)-
()-Linalool, for example, occurs at a concentration of 80–85% in Ho
oils from Cinnamomum camphora; rosewood oil contains about 80%. (3S)-(+)-
Linalool makes up 60–70% of coriander oil (“coriandrol”).
Linalool is used frequently in perfumery for fruity notes and for many
floral fragrance compositions (lily of the valley, lavender, and neroli). Because of its
relatively high volatility, it imparts naturalness to top notes. Since linalool is stable
in alkali, it can be used in soaps and detergents. Linalyl esters can be prepared from
linalool.Most of the manufactured linalool is used in the production of vitamin E.
Physical properties
Properties. Racemic linalool is, similarly to the individual enantiomers,
a colorless liquid with a floral, fresh odor, reminiscent of lily of the valley.
However, the enantiomers differ slightly in odor. Together with its esters,
linalool is one of the most frequently used fragrance substances and is produced
in large quantities. In the presence of acids, linalool isomerizes readily to geraniol,
nerol, and α-terpineol. It is oxidized to citral, for example, by chromic acid. Oxidation
with peracetic acid yields linalool oxides, which occur in small amounts
in essential oils and are also used in perfumery. Hydrogenation of linalool gives
tetrahydrolinalool, a stable fragrance material. Its odor is not as strong as, but
is fresher than, that of linalool. Linalool can be converted into linalyl acetate by
reaction with ketene or with an excess of boiling acetic anhydride.
Occurrence
The optically active forms (d- and l-) and the optically inactive form occur naturally in more than 200 oils from
herbs, leaves, flowers and wood; the l-form is present in the largest amounts (80 to 85%) in the distillates from leaves of Cinnamomum
camphora var. orientalis and Cinnamomum camphora var. occidentalis and in the distillate from Cajenne rosewood; it also has been
reported in champaca, ylang-ylang, neroli, Mexican linaloe, bergamot and lavandin; a mixture of d- and l-linalool has been reported
in Brazil rosewood (85%); the d-form has been found in palmarosa, mace, sweet orange-flower distillate, petitgrain, coriander (60
to 70%), marjoram and Orthodon linalooliferum (80%); the inactive form has been reported in clary sage, jasmine and Nectandra
elaiophora. Also reported found in over 280 products including apple, citrus peel oils and juices, berries, grapes, guava, celery, peas,
potato, tomato, cinnamon, cloves, cassia, cumin, ginger, mentha oils, mustard, nutmeg, pepper, thymus, cheeses, grape wines, butter,
milk, rum, cider, tea, passion fruit, olive, mango, beans, coriander, cardamom and rice.
Uses
Linalool is one of the allergens of Ylang-Ylang oil
(extract from Cananga odorata).
Uses
linalool is a fragrant component of both lavender and coriander. It can be incorporated into cosmetics for perfuming, deodorant, or odor-masking activity.
Definition
ChEBI: A monoterpenoid that is octa-1,6-diene substituted by methyl groups at positions 3 and 7 and a hydroxy group at position 3. It has been isolated from plants like Ocimum canum.
Preparation
In the 1950s, nearly all linalool used in perfumery was isolated from
essential oils, particularly from rosewood oil. Currently, this method no longer
plays a commercial role.
Since linalool is an important intermediate in the manufacture of vitamin E,
several large-scale processes have been developed for its production. Preferred
starting materials and/or intermediates are the pinenes and 6-methyl-5-hepten-
2-one. Most perfumery-grade linalool is synthetic.
1) Isolation from essential oils: Linalool can be isolated by fractional distillation
of essential oils, for example, rosewood oil and coriander oil, of which Brazilian
rosewood oil was the most important.
2) Synthesis from α-pinene: α-Pinene from turpentine oil is selectively hydrogenated
to cis-pinane, which is oxidized with oxygen in the presence of
a radical initiator to give a mixture of about 75% cis-pinane and 25% transpinane
hydroperoxide.The mixture is reduced to the corresponding pinanols
either with sodium bisulfite (NaHSO3) or with a catalyst. The pinanols can
be separated by fractional distillation and are pyrolyzed to linalool: ()-α-
pinene yields cis-pinanol and (+)-linalool, whereas ()-linalool is obtained
from trans-pinanol.
3) Synthesis from -pinene: For a description of this route, see under Geraniol.
Addition of hydrogen chloride to myrcene (obtained from β-pinene) results in a mixture of geranyl, neryl, and linalyl chlorides. Reaction of this mixture
with acetic acid–sodium acetate in the presence of copper(I) chloride gives
linalyl acetate in 75–80% yield. Linalool is obtained after saponification.
4) Synthesis from 6-methyl-5-hepten-2-one:The total synthesis of linalool starts
with 6-methyl-5-hepten-2-one; several large-scale processes have been developed
for synthesizing this compound:
a. Addition of acetylene to acetone results in the formation of 2-methyl-3-
butyn-2-ol, which is hydrogenated to 2-methyl-3-buten-2-ol in the presence
of a palladium catalyst.This product is converted into its acetoacetate
derivative with diketene or with ethyl acetoacetate. The acetoacetate
undergoes rearrangement when heated (Carroll reaction) to give
6-methyl-5-hepten-2-one:
b. In another process, 6-methyl-5-hepten-2-one is obtained by reaction of
2-methyl-3-buten-2-ol with isopropenyl methyl ether followed by a
Claisen rearrangement:
c. A third synthesis starts fromisoprene, which is converted into 3-methyl-2-
butenyl chloride by addition of hydrogen chloride. Reaction of the chloride
with acetone in the presence of a catalytic amount of an organic base
leads to 6-methyl-5-hepten-2-one:
d. In another process, 6-methyl-5-hepten-2-one is obtained by isomerization
of 6-methyl-6-hepten-2-one.The latter can be prepared in two steps
from isobutylene and formaldehyde. 3-Methyl-3-buten-l-ol is formed in
the first step and is converted into 6-methyl-6-hepten-2-one by
reaction with acetone. 6-Methyl-5-hepten-2-one is converted into linalool in excellent yield by base-catalyzed ethynylation with acetylene
to dehydrolinalool. This is followed by selective hydrogenation of
the triple bond to a double bond in the presence of a palladium carbon
catalyst.
Aroma threshold values
Detection: 4 to 10 ppb
Taste threshold values
Taste characteristics at 5 ppm: green, apple and pear with an oily, waxy, slightly citrus note.
General Description
Linalool is a monoterepene compound. It is the major component of many essential oils. Anti-inflammatory properties of () linalool, a naturally occurring enantiomer, has been studied. It is also the major constituent of the basil and thyme essential oil and its anti-microbial effect was determined using the agar well diffusion assay. Linalool is reported to have dose-dependent marked sedative effects at the central nervous system (CNS), including hypnotic, anticonvulsant and hypothermic properties. Linalool is reported to have a lemon like odor.
Contact allergens
Linalool is a terpene chief constituent of linaloe oil,also found in oils of Ceylon cinnamon, sassafras,orange flower, bergamot, Artemisia balchanorum, ylang-ylang. This frequently used scented substance is a sensitizer by the way of primary or secondary oxida-tion products. As a fragrance allergen, linalool has to be mentioned by name in cosmetics within the EU
Pharmacology
l-Linalool showed no sedative action in the mouse motility test when injected
ip at a dose of 100 mg/kg (Binet, Binet, Miocque, Roux & Bernier, 1972). but Wagner & Sprinkmeyer
(1973) reported that linalool depressed spontaneous motility of mice at doses of 31-6 and 100 mg/kg.
Linalool showed spasmolytic action against carbachol-, histamine- and barium chloride-induced
contractions in isolated guinea-pig ileum, the ED50 being about 100-200 mg/litre (Wagner & Sprinkmeyer.
1973). and in the isolated rat duodenum, contractions caused by 0.05 /ig acetylcholine/ml
were inhibited by 50% by 10 μg l-linalool/ml (Binet et al. 1972). Linalool showed slight papavarinelike
and very slight atropine-like antispasmodic action on small intestine isolated from the mouse
(Imaseki & Kitabatake, 1962).
In studies carried out by Atanassova-Shopova et al. (1973), the ED50 for preventing tonic hyperextension
of the hind limbs of rats from electric shock was found to be 135 mg/kg given ip. Linalool
had a marked anticonvulsive and protective effect on pentylenetetrazol convulsions in mice at 150,175 and 200 mg/kg and in rats at 200 and 300 mg/kg. It showed a slight antistrychnine effect
in mice at high and toxic doses (300 mg/kg), reduced motor activity of mice at 100 mg/kg, and
at 50 mg/kg slightly decreased the motor activity of amphetamine- or caffeine-stimulated mice.
The TD50 (neurotoxic dose) of linalool for influencing motor co-ordination of mice in the Rota-rod
test was found to be 178 mg/kg. Linalool at doses of 50 or 100 mg/kg prolonged the narcotic effects
of hexobarbitone, alcohol and chloral hydrate.
The equilibrium and spontaneous or reflex activity of the goldfish, Carassium auratus, was disturbed
by exposure to aquarium water containing a 0-13 ml/litre concentration of a suspension
containing 1 ml linalool plus 9 ml of a 10% aqueous solution of Tween 80, and the agressiveness
of the male fighting fish, Betta splendens, was only very slightly inhibited by exposure to aquarium
water containing 0-3 ml of the same suspension of linalool/litre (Binet, 1972).
Linalool and other terpene alcohols were found to be useful in man as sedatives and spasmolytics
when administered in doses of 0.01-1 g, the effects having been tested in mice, goldfish, and rats
(Laboratoires Meram, 1966).
Linalool depressed frog-heart activity in doses above 0-2 mg/g (Lysenko, 1962). Vasodilation by
direct action of linalool upon the blood vessels was demonstrated by Northover & Verghese (1962).
An iv dose of 9.2 mg/kg was required to produce a 25% fall in systolic arterial blood pressure
in the anaesthetized dog and a hypotensive response was also observed in the decerebrated and
despinalized dog. A dose of 0.05 g in fluid perfusing the leg of an anaesthetized dog or the isolated
ear of a rabbit produced a maximum increase of 120% or 90%, respectively, in venous outflow
over pre-injection values. Linalool dilated the small blood vessels of the exposed mesorchium of
the anaesthetized mouse, lowering the threshold for electronic stimulation. Incubation of human,
bovine and canine aortae in 015 M-linalool failed to stabilize the structure of the aortic wall proteins
against hydrothermal shrinkage (Milch, 1965). Linalool inhibited incorporation of acetic acid or
mevalonic acid into total or digitonin-precipitable nonsaponifiable lipids by rat-liver homogenates
(Gey, Pletscher, Isler, Riiegg, Saucy & Wiirsch, 1960).
Anticancer Research
Studies of antitumor activities and toxicity were done on solid S-180 tumor-bearingSwiss albino mice. It results in an induction of oxidative stress with an antitumoractivities result. In comparison with cyclophosphamide, antioxidant effects wereobserved in the liver and modulation of proliferation of spleen cells in tumor-bearingmice challenged with lipopolysaccharides, while both were seriously affected bycyclophosphamide (Costa et al. 2015).
Synthesis
It can be prepared synthetically starting from myrcene or from dehydrolinalool; it can be obtained by fractional distilla tion and subsequent rectification from the oils of Cajenne rosewood (Licasia guaianensis, Ocotea caudata), Brazil rosewood (Ocotea
parviflora), Mexican linaloe, shiu (Cinnamomum camphora Sieb. var. linalooifera) and coriander seeds (Coriandrum sativum L.).
Metabolism
The metabolism of 14C-labelled linalool in the rat
was studied by Parke, Rahman & Walker (1974a). An
intragastric dose of 500 mg linalool/kg body weight
was largely (93%) excreted within 72 hr in the urine
(55%), faeces (23%) and expired air (15%). The
radioactivity remaining after 72 hr was located
mainly in the liver (0-5%), gut (0-6%), skin (0-8%)
and skeletal muscle (1-2%). Rapid urinary excretion
indicated that linalool was rapidly absorbed from the
gut, while delay in excretion in the expired air
suggested that linalool might enter intermediary
metabolism and also be metabolized by conjugation in
the bile and urine. Ip administration of 20 mg
linalool indicated that enterohepatic circulation
occurred, resulting in a short-term metabolic load on
the liver and delayed faecal excretion. The
metabolism of large doses in the rat, with rapid
excretion of linalool and its metabolites, suggests
no long-term hazard from tissue accumulation on
chronic exposure to concentrations normally
encountered in foods, although enterohepatic
circulation might prolong the metabolic load on the
liver over a relatively short period. A study of the
effects of linalool and other terpenoids on hepatic
drug-metabolizing enzymes suggested that these
compounds induce the enzymes involved in their own
metabolism. Linalool, which is metabolized by
reduction and conjugation with glucuronic acid,
increased the activity of 4-nitrobenzoate reductase
but did not increase other enzymes studied (Parke &
Rahman, 1969). Linalool can be metabolized by micro-
organisms. l-Linalool was partially oxidized by
incubation with Aspergillus nig er (Goto, 1967). The
linalool content of grape essential oil decreased
during must fermentation and wine formation
(Rodopulo, Egorov, Bezzubov, Kormakova & Megrelidze,
1972). A strain of Pseudomonas pseudomallei, isolated
from soil, metabolized linalool with the formation of
camphor, 4-methyl-4-vinylbutyrolactone, 4-methyl-
trans-3-hexenoic acid, and 2,6-dimethyl-6- hydroxy-
trans-2,7-octadienoic acid (Mizutani, Hayashi, Ueda &
Tatsumi, 1971).
