Limonen

• Nama sistematika : 4R)-(+)-1-Metil-4-(1-metiletenil)sikloheksen

Dari minyak asiri jeruk (Rutaceae)

C10H16, Mr 136.23
Cairan tidak berwarna, td 177-178°C,
Nama lain:
D-(+)-Limonen, (+)- -Limonen, (+)-
Citrus nobilis Dipenten, (R)-p-Menta-1,8-dien
• Minyak asiri dihasilkan oleh tumbuh-tumbuhan khususnya
kelompok jeruk-jerukan (Rutaceae), seperti C. aurantifolia, C.
sinensis, C. nobilis, C. hystrix, C. limon.
• Minyak asiri terdapat di dalam kelenjar minyak di bagian dalam
kulit.
• Minyak asiri dapat diperoleh dari tanaman dengan cara pressan
dingin, ekstraksi pelarut, destilasi uap.
• Semua minyak asiri Citrus mengandung komponen utama (4R)-
(+)-limonen atau D-(+)-limonen. Campuran rasemat dari kedua
enansiomer ini disebut dipenten. Rasemat diperoleh dengan
pemanasan salah satu dari enansiomer (4R)-(+)-limonene
sampai 300 °C.
• (4R)-(+)-Limonen digunakan di industri makanan, minuman,
dan kosmetik sebagai aditif pemberi rasa dan aroma.
• Limonen telah ditemukan sebagai pelarut yang sangat baik,
karena sifatnya yang lebih biodegradable daripada
pembersih dengan dasar destilat minyak mineral seperti
naphtha, yang terdiri atas alkana. Pelarut biogenik yang
dapat diakses dari sumber terbarukan. Daya pelarutan cukup
tinggi. Ini juga digunakan sebagai pengencer untuk pernis.
Memiliki bau yang dapat diterima bagi konsumen.
• Stabilitas kimia terbatas. Limonen rentan terhadap asam dan
basa. Reaksi yang paling umum ketika disimpan dengan cara
yang tidak benar adalah autoksidasi menjadi enansiomer
carvon.
 Isolasi

Prinsip
• Sumber yang cocok untuk isolasi (R) - (+) - limonen adalah
minyak jeruk manis diperoleh dengan memeras kulit jeruk,
sebagai produk sampingan dari pembuatan jus jeruk.
• Untuk mendapatkan (4R) - (+) - limonen murni dipisahkan
dengan distilasi fraksinasi vakum. Meskipun limonen cukup
stabil secara termal untuk disuling pada tekanan ambien,
dianjurkan untuk melakukan fraksinasi vakum.
Metode
Minyak jeruk manis Brasil (36 g) mengandung 90% (R) - (+) - limonen
didistilasi fraksionasi vakum pada 1000 Pa dengan suhu keluar 120°C.
Kolom Vigreux 10 cm digunakan dan distilasi dijalankan agak perlahan.
Dua fraksi yang diperoleh jernih dan tidak berwarna dengan bau yang
tidak seberat pada buah jeruknya.

Tabel Hasil destilasi

td pada nD
Fraksi Berat (g) Penggunaan
1000 Pa (°C) pada 24 °C
I 25 44 4.0 1.4708 Dibuang
II 40 44 23.0 1.4708 Redestilasi
Pemurnian
Sebanyak 17,0 g fraksi II diredistilasi secara perlahan dengan peralatan
yang sama tetapi dengan kolom Vigreux yang lebih panjang 30 cm.

Tabel Hasil destilasi

td pada nD pada
Fraksi Berat (g) Penggunaan
900 Pa (°C) 24 °C
Analisis
I 42 43 1.4 1.4696
NMR
II 42 43 14.8 1.4702 disimpan
Analisis
III 43 44 0.8 1.47
NMR
Spektra

Spektrum UV memperlihatkan pita serapan tunggal dengan bahu sekitar 207

nm karena dua ikatan ganda yang terisolasi. Tidak ada struktur halus vibrasi
yang terlihat. Pita CD absorpsi positif, tetapi sangat lemah.
 =CH

CH C=C

The IR spectrum shows CH vibration bands for both sp2 and sp3 hybridized CH fragments. The frequency
of the small sharp peak at 3100 cm 1 is indicative of a terminal =CH2 group. In addition, a sharp C=C
vibration can be seen at 1630 cm 1.
 CH3

=CH2

The discussion of the 1H NMR spectrum starts with the observation of the two olefinic
signals with an intensity ratio of 1:2, indicating that even at 400 MHz the signals of the
two olefinic protons at C-9 are not separated from each other. The two methyl group
signals are clearly separated, although they are attached to a similar double bond. The
other proton signals are difficult to assign using only the 1H spectral information.
 CH3-C7, C10
CH-C4
CH-C2

Cq-C1, C8 CH2-C9
CH2-C3, C5, C6

The signals of the two proton-bearing olefinic carbon atoms C-2 and C-9 are immediatedly assigned due to
their sign in the APT spectrum. The safe assignment of the two corresponding quaternary olefinic carbon
atoms C-1 and C-8 can be obtained by using shift increments or can be assured from the HMBC spectrum.
Two of the methylene carbon atoms resonate very close together at 30.7 ppm; one further me-thylene carbon
atom signal appears at 28 ppm. Finally, the positive signal in the APT spectrum at 41 ppm must be from C-4,
being the only aliphatic methine carbon atom in the molecule. With the help of the HSQC spectrum, therefore,
The two expansions of the HMBC spectrum first confirm the assignment of the quaternary olefinic carbon atoms C-1
and C-8, since H-9 shows a correlation signal to the carbon atom at 150.3 ppm, whereas H-7 shows a weak connection
to the carbon signal at 133.7 ppm. H-9, of course, shows three bond correlations to C-4 and C-10. Both H-5 show a two-
bond correlation to C-4; very important is the assignment’s confirmation due to the correlation of one of the H-5 signals
at 1.8 ppm with C-1.
Questions
• Limoneneisaterpeneconsistingoftwoisopreneunits.Markthesetwobuildingbl
ocksinthelimonene formula.
• Suggest a reason for the good solubility properties of the racemic limonene
dipentene. Compare the dissolution properties of alkanes, cycloalkanes,
alkenes and aromatic compounds such as benzene and toluene.
• Limonene, as a monoterpene, is in principle made up of two isoprene
units. Give the names of two natural isoprene polymers.
• Make a suggestion why dipentene used for cleaning purposes is more
easily biodegradable than mineral oil distillates.
 C10H20O, MW 156.26
Colourless crystals,
From the essential oil peppermint mp 40-42 °C, [ ] –50.7°
25 D

Mentha arvensis var. piperascens L. Menthol is commercially available.

(Lamiaceae) Synonymous names:
Menthyl alcohol, p-Menthan-3-ol
• Peppermint oil is used in industry in its entirety due to its marvellous
flavour and it is not as rich in menthol content as other oils.
• (–)-menthol is at position 2 in the market of flavourings
• Menthol, a monocyclic monoterpene secondary alcohol, is biosynthe-
sized from limonene by stepwise oxidation and two hydrogenations.
Hence, the intermediates of this biosynthetic pathway, i.e.
piperitenone, piperitone, its isomer pulegone, and menthone, are
always companions in any (–)-menthol-producing plants.
• The essential oil may be obtained from above-ground plant material by
classical steam distillation or by a modern destraction process with
supercritical carbon dioxide.
• It is a rather viscous, destraction colourless liquid with a rich (–)
menthol content (up to 90%).
• The first demand for such an approach was that it had to supply only
the “natural” (–)-enantiomer of menthol because its organoleptic
properties (cool, fresh, minty, sweet).
• (+)-menthol (weaker cool and minty, but musty, phenolic and bitter).
The odour threshold for (–)-menthol is 1 ppm.
• The solubility in water is slight (below 1 g/L), but this is sufficient for
all applications.
• In addition to its attractive smell, natural menthol has numerous
external and internal medical applications, some of which everbody
has already made use of.
• A typical feature of menthol is, that on rubbing it on the skin in the
form of a cream, it causes a pleasant sensation of cold. This is used
for local anaesthetic and analgesic effects, e.g. to relieve pain from
muscle cramps or headaches, even from migraine headache.
• An ethanolic solution of menthol has an antiseptic effect, and it acts
also as an insect repellent. Menthol preparations with up to 1% content
act as an antipruritic and reduce itching, whereas at higher
concentrations just the counter-irritant effect sets in.
Isolation
Principle
• The source for the isolation of (–)-menthol is not peppermint oil but a
steam distillate called Japanese peppermint oil of a related plant,
named Mentha arvensis var. piperascens L., which has a 70% (–)-
menthol content.
• The method used for separation is simple and it is the historically
long known one: deep cooling of the essential oil causes
crystallization of (–)-menthol.
• On standing in a normal refrigerator, crystallization does not occur
and only turbidity can be observed.
• When cooled to –18 °C (–)-menthol crystallizes in the form of a felted
mass. Crystallization is possible both due to the high content of (–)-
menthol in the oil and the fact that (–)-menthol as an alcohol has the
ability to form hydrogen bonds to other menthol molecules.
Method
• A flask containing 110g of colourless 70% peppermint oil is stored
overnight in a deep freezer at –18 °C.
• (–)-Menthol crystallizes and the impression arises that all of the
material has solidified. This is proven to be untrue when a spatula is
pressed on the surface of the material, showing a flexible mass with
liquid parts still in the flask.
• Therefore, the flask is allowed to stand for another day in a normal
refrigerator at +4 °C.
• The mass in the flask is now a mixture of solid (–)-menthol and a
liquid which is separated by suction filtration through a sintered glass
filter funnel.
• The portion of colourless crude (–)-menthol has a mass of 8.3 g and
the filtrate a mass of 101.7 g. The filtration requires some time due to
the high viscosity of the liquid portion.
Purification
• The crude (–)-menthol is dissolved in a flask at room temperature
by shaking it with n-hexane (25 mL).
• The flask is stoppered and allowed to stand in a deep freezer
overnight, causing crystallization of (–)- menthol as colourless
needles.
• Filtration gives the pure compound (mass 3.2 g) with mp 40 42 °C,
which is in accordance with reference data, and an optical rotatory
power of [ ] –50.7° (c 0.050 g/mL, ethanol).
25 D
Questions
1. (–)-Menthol is an example of a most stable stereoisomer. Draw the
structures of all eight possible stereoisomers with the constitution of 5-
methyl-2-(1-methylethyl)cyclohexanol in their chair conformation
(perspective view) and explain the reason why (–)-menthol is the most
stable.
2. Ascertain the complete description of the configuration for all isomers
according to the R/S- nomenclature. If you want, you can use the full
description given on the first page of this chapter for (–)-menthol to
accomplish this easily. Correlate the name menthol and the names of the
other isomers isomenthol, neomenthol, and neoisomenthol with your
3. How can one determine whether (+) or (–) has to be assigned to a given
structure?
 (1R,4S,4aS,6R,8aS)-Octahydro-4,8a,9,9-tetramethyl-
1,6-methanonaphthalen-1(2H)-ol

C15H26O, MW 222.36
Colourless plates, mp 56 °C, bp 266 271 °C
[ ] 22 119° (c 0.1 g/mL, chloroform)
Patchouli alcohol is commercially available.
Synonymous names:
Pogostemon cablin Benth. (Lamiaceae)
(–)-Patchouli alcohol, (–)-Patchoulol, Patchoulol
• Steam distillation of the leaves Pogostemon cablin of gives rise to patchouli as the
essential oil. This distillation may be done with fresh leaves close to a plantation
(preferably) or elsewhere with dried and in this state exported leaves. The yield of
essential oil is astonishingly high: only 35–50 kg of fresh leaves yield 1 kg of
patchouli. A main component of the viscous oil is patchouli alcohol (patchoulol).
• The scent of patchouli is absolutely characteristic, intense, lasting and not to
everyone’s liking.
• Traders used to pack these goods together with some patchouli leaves to prevent
moths from laying their eggs between the fabrics. Thus, patchouli was used as a
natural insect repellent.
• In Asia, the patchouli plant is used as a medicinal herb with antifungal, antiseptic
and antirheumatic effects. The insecticidal use to protect clothing from webbing
clothes moths and silverfishes was already mentioned above.
• Patchouli alcohol is a tricyclic tertiary sesquiterpene alcohol.
Isolation
Principle
• It is really difficult to isolate pure patchouli alcohol from patchouli as a source. The
problem is that patchouli consists of ca. 50% patchouli alcohol (C15H26O) and a mixture of
structurally very similar sesquiterpenoid compounds, e.g. patchoulenol (C15H24O),
patchoulenone (C15H22O), norpatchoulenol (C14H22O), nortetrapatchoulol (C14H22O), alfa-
patchoulene (C15H24), beta-patchoulene (C15H24), seychellene (C15H24), alfa-guajene
(C15H24) and alfa-bulnesene (C15H24).
• The molecular formulae give an idea of the similarities in the vapour pressure of these
compounds. Furthermore, such relatives form eutectic mixture, which induces a reduced
tendency for the crystallization of a single compound.
• Although patchouli used for this isolation was stored over a longer period of time in a
refrigerator, no crystallization was observed. However, TLC shows that patchouli alcohol
is the most polar of these compounds (smallest Rf value).
Method
• Patchouli (80 g) is placed in a 100 mL round-bottomed flask and
distilled using a rotary vane vacuum pump over a 20 cm
Vigreux column. Nine fractions are made.
• Fractions 2-8 are allowed to stand overnight first in a normal
refrigerator (15°C) and then in a deep cooling refrigerator (80
°C).
• In no case does crystallization occur. n-Hexane is added to
each fraction in a 1:1 ratio and the samples are again cooled to
–80 °C in stoppered flasks.
• In no case does crystallization occur. The hexane is removed in
vacuo, replaced by pentane and the procedure repeated with
the same result. The pentane is removed and GC MS data are
taken from fractions 2, 5 and 9. Data for fraction 9 (base peak
and fragments) give a hint that patchouli alcohol is present.
• The TLC behaviour of fraction 9 is tested with five eluents: n-hexane,
methanol, n-hexane ethyl acetate (1:1), dichloromethane and
chloroform. The last shows the best differentiation of spots on the
plate with an R value for patchouli alcohol of 0.20 as the slowest
spot.
• For detection, the TLC alumina foils are dipped into vanillin reagent
and the spots are visualized by careful heating in the hot air stream
from a heat gun. (Recipe for the reagent: dissolve 15 g of vanillin in
200 mL of ethanol and add 2 mL of concentrated sulfuric acid. Handle
with care.).
Purification

Step 1: by preparative column chromatography:

• Fraction 9 (3.4 g) is subjected to column chromatography under the
following conditions: stationary phase, silica gel 60 (0.040 0.063 mm);
eluent, chloroform; column dimensions, 60 × 3 cm.
• The fractions containing patchouli alcohol are identified by TLC and
combined. The solvent is removed on a rotary evaporator and the
colourless oily residue is allowed to stand at –15 °C overnight.
• The residue solidifies to yield 952 mg of colourless crystals. The purity is
estimated from an 1H NMR spectrum to be about 90%.
Step 2: by preparative RP-HPLC:
• A 250 mg amount of the enriched patchouli alcohol from above is
subjected to separation by preparative RP-HPLC under the following
conditions: Vertex column Eurospher 100-C18 (5 m); eluent, methanol; UV
detector (210 nm); flow rate, 2 mL/min; sample amounts in the range 13–
21 mg in 100 L of solution.
• The retention time of patchouli alcohol is 23.5 min under these conditions.
• The fractions containing the pure patchouli alcohol are collected,
combined and the solvent is removed.
• All spectra shown here were measured with this material.