Subject: Safrole FAQ update - safrolefaq.txt (1/1)
Date: Sun, 10 Oct 1999 20:13:30 -0700 (PDT)
From: cherriebaby@hushmail.com
To: Rhodium <rhodium@anon.nymserver.com>

File: SAFROLE.FAQ
Ver : 0.1
Rev : alpha-test, 02 September 1999
Stat: preliminary/RFC
Size: 36900 bytes.
Cont: Almost everything you wanted to know about safrole
Edit: <p r e d a t o r> ... product of Australia

Cont: 1) Source plants and percentages (where available)
      2) Physical and chemical properties
      3) Extraction and refinement procedures
      4) Characterisation and derivatives
      5) Commercial sources (if you think it's worth the risk)
      6) Some references.

Aim : to render fascist governmental purchase restrictions irrelevant,
      by providing information concerning natural and unregulated sources.

Note: has been stripped down of stuff unrelated to safrole or isosafrole
      in the precursor documents.

-----------------------------------------------------------------------------
1) Safrole is everywhere. Source plants.

-----------------------------------------------------------------------------

This list is not meant to be exhaustive. Further data would be welcome.

 Plant                                  Plant part/extract, safrole
percentage

 Acorus calamus                         (origin and % unknown)
 Angelica polymorpha                    (oil, origin and % unknown)
 Asari seiboldii                        (origin and % unknown)
 A. sieboldii var. seoulense            (origin and % unknown)
 Asari forbesii                         (origin and % unknown)
 Asari inflatum                         (origin and % unknown)
 Asari magnificum var dinghugense       (origin and % unknown)
 Asari caudigerum var cardiophyllum     (origin and % unknown)
 Atherosperma moschatum                 (bark oil, % unknown)
 Cananga odorata (Ylang Ylang)          (isosafrole : origin and % unknown)
 Cinnamomum burmannii                   (China, leaf/twig oil, 97-99%
safrole)
 Cinnamomum camphora                    (root bark oil, 50-80% safrole)
  var Yu-Sho Hangchow (China)           (wood oil, 2.9% safrole)
  var Yu-Sho Kiukiang (China)           (wood oil, 0.8% safrole)
  var Yu-Sho Nanchang (China)           (wood oil, 1.7% safrole)
  var Hon-Sho (Japan)                   (wood oil, 18.1% safrole)
  var Ho-Sho  (China)                   (wood oil, 0.2% safrole)
      Ho-Sho  (Formosa)                 (wood oil, 7.8% safrole)
 Cinnamomum iners                       (Malaysia, wood oil, high % safrole)
 Cinnamomum micranthum                  (wood oil, 95% safrole)
 Cinnamomum oliveri                     (bark oil, % unknown)
 Cinnamonum parthenoxylon               (wood oil, Nees variety, 80%
safrole)
 Cinnamomum paucifolium                 (China, leaf oil, 68-90% safrole)
 Cinnamomum petrophilum                 (China, leaf oil, 97% safrole)
 Cinnamomum rigidissum                  (China, wood oil, high % safrole)
 Cinnamomum verum ("Ceylon Cinnamon")   (origin and % unknown)
 Curuma amada                           (steam-dist rhizome oil, 9.3%
safrole)
 Doryphora aromatica                    (bark oil, % unknown)
 Doryphora sassafras                    (leaf oil, % unknown)
 Eremophila longifolia                  (leaf oil, % unknown)
 Hamamelis virginiana                   (0.5% of essential oil)(Witch Hazel)
 Illicium parviflorum Michx             (origin unknown, 90% safrole)
 Illicium religiosum (illiciacea)       (leaf oil, % unknown)
 Illicium verum                         (Star Anise... disputed)
 Juniper virginiana                     (leaf oil, 11% safrole, 6%
isosafrole)
 Magnolia salicifolia (magnoliaceae)    (origin and % unknown)
 Myristica fragrans                     (volatile seed oil, 0.2-0.6%
safrole)
 Nemuaron humboldtii                    (bark oil, % unknown)
 Ocimum basilicum (labiatae)            (leaf juice, trace, % unknown)
 Ocotea cymbarum                        (wood oil, 84-93% safrole)
 Ocotea pretiosa                        (S America and % unknown)
 Piper auritum                          (Central America: leaf oil, 70%
safrole)
 Piper callosum                         (Brazil: leaf oil, 70% safrole)
 Piper hispidinervium                   (Brazil: leaf oil, 81-88% safrole)
 Piper nigrum                           (black pepper, trace, % unknown)
 Sassafras albidum                      (wood oil, 80-85% safrole)
 Theobroma cacao                        (origin and % unknown)
 Umbellularia californica               (leaf oil, % unknown)(Calif
Sassafras)
 Zieria smithii                         (steam-distilled leaf oil, %
unknown)

 Oil of massoira bark (?) reputedly yields about 14% safrole.

-----------------------------------------------------------------------------
A major source: CAMPHOR LAUREL ROOT : Cinnamomum Camphora

-----------------------------------------------------------------------------

C. camphora is a pest xenophyte tree species now at plague proportions in
regions such as northern NSW. They exude chemicals via their roots, into the
soil, which kills worms and other soil biota; via their leaves which kill
aquatic organisms near leaf-drop regions, and their berries sterilise the
birds which eat them. They can live for over 1200 years.
The canonical work on camphor and safrole production from this tree was
performed by Dr Teikichi Hiraizumi, President of Takasago Chem Industry Co,
Tokyo, and can be found in the essential oils work by Guenther.

CAMPHOR OIL is obtained by steam distillation of the wood of the camphor
tree Cinnamonum camphora Sieb. (Lauraceae) growing in China, Taiwan, Japan
[and Australia, where it is classed as a noxious weed]. The main constituent
of the crude oil is camphor (ca. 50%) which can be separated by cooling and
centrifugation.

Fractionation of the mother liquor gives two oils:
1) White camphor oil is the first distillation fraction (ca 20% of the crude
   camphor oil). It is a colourless or nearly colourless liquid with a
   cineole-like odour.

2) Brown Oil of camphor is a fraction with a boiling point higher than
   that of camphor (ca. 20%) It is a pale yellow to brown liquid with the
   odour of sassafras oil.

   Density 1.064-1.075; Optical rotation [ND20] 1.51 - 1.55
   [alpha]d 0 to +3°. Flash point 6°C.
   Solubility 1 vol in 2 vols of 90% ethanol.

   The oil contains more than 80% safrole and, like Brazilian sassafras oil,
   is therefore used as raw material for the production of piperonal via
   isosafrole. Camphor oils with a high safrole content can also be obtained
   by steam distillation of the wood of Cinnamonum parthenoxylon Nees.

Three Varieties of camphor oils are produced.

+---------------------------------------------------------------------------+
| Formosan Camphor oils | camphor-linalool and camphor-safrole types.
|
| Japanese Camphor oils | camphor-safrole types.
|
| Chinese  Camphor oils | cineole-terpineol-camphor (Apopin Oil) type.
|

+---------------------------------------------------------------------------+
Camphor oil "true" is produced by the steam distillation of the wood,
rootstumps and branches of the type of Cinnamonum Camphora known as Hon-Sho,
which grows in Formosa and Japan. [Ed Note: Hon-Sho oil holds 18.1% safrole)

Along with the crude oil comes a solid, partly crystalline mass of crude
camphor. The oil is separated from the crude camphor by filterpressing. This
yields crude camphor oil. The crude oil is subsequently fractionally
distilled
under vacuum, and yeilds another 50% of crude camphor. The remaining 50% of
filterpressed crude camphor oil is now free of camphor. It contains light
terpenes, cineole, safrole, terpineol, sesquiterpenes, and sesquiterpene
alcohols. These are separated into various fractions known as:

+-----------------------------------------------------------------------+
| White Camphor oil | The light fraction, containing cineole and        |
|                   | monoterpenes.                                     |
|-------------------+---------------------------------------------------|
| Brown Camphor oil | The medium heavy fraction containing up to 80%    |
|                   | of safrole and some terpineol.                    |
+-----------------------------------------------------------------------+

  [Extended Monograph]
  Brown oil of camphor is the medium heavy fraction from vacuum distillation
  of the camphor-free oil (aka white oil, filterpressed and camphor-free).
  Brown camphor oil amounts to 6 or 7 percent of the total oil, or 20-22%
  of the decamphorised oil. Brown oil is produced almost entirely in
  Formosa and Japan, from the Hon-Sho type of cinnamomum camphora, the
  camphor tree.

  This fraction is most interesting from the perfumer's point of view. Its
  main constituent is safrole, and the redistilled brown camphor can be used
  directly in soaps for its magnificent masking effect. The safrole can be
  isolated from the oil and used as a starting material for heliotropine,
  vanillin and other perfume materials. Terpineol is also separated during
  the safrole-isolation and serves as is or may be transformed into terpinyl
  esters.

  An artificial sassafras oil, "Oil Camphor Sassafrassy" is also produced
  from the brown oil by rectification and adjustment of the content of
  safrole, terpenes, etc.

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                      JUNIPER leaves - juniper virginiana

-----------------------------------------------------------------------------

Table below: representative volatile leaf oil composition for junipers
(J. virginia var virginiana (USA), eluted from a DB-5 gas chromatography
column. Data expressed in % of total oil, the oil derived from steam
distillation of the FOLIAGE. (so no digging-up of the roots is required).

This gave us a list of approximately 140 distinct molecules which came off
the column, I left most of them off.

The significant numbers are marked with a ***

 RT(s)   Compound             %        B.P. (deg C)  from Merck, 12th edn.
 -------------------------------------------------------------------------
 319      alpha-pinene       1.4       bp20:52.5  bp760:155-156
 379      sabinene           6.7       No Listing
 408      myrcene            0.9       beta from: bp10:44
 481      limonene          18.9       bp763:175-176
 608      terpinolene        0.5       No Listing
 632      linalool           4.4       (dl) 194-197
 734      camphor            3.7       mp:179  bp204
 789      borneol            0.8       mp:(d)208 (l):204 bp:(d) 212:(l) 210
 820      4-terpineol        1.5       bp:206-219 (d, l, and dl)
 1101 *** safrole           10.9       mp:~11  bp:232-234
 1229 *** cis-isosafrole     6.7       mp:~8.2 bp760:253 bp100:179.5
 1403     methyleugenol      2.9       No Listing
 1700     delta-cadinene     0.8       bp9:124

RT = retention time on the DB-5 column.

I gather this tree is known as the Red Cedar, though I think there are
probably several trees which come under this moniker so there is room for
confusion. It is also supposed to be the source of Red Cedarwood Oil, though
the safrole content of this is unknown. Cedarwood oil is used for immersion
lenses in high-magnification microscope work.

Note: the incompetants at AUROMA Australia will supply you with the leaf oil
of the communis species when you ask for the virginiana type. Ellisons of
Nowra sell the seeds to this plant, which have reliably germinated.

*****************************************************************************
                                 SASSAFRAS

*****************************************************************************

There are numerous members of the sassafras family.

A guide to the safrole content sassafras oil is its congealing point.
Accuracy is approximatey 2%

% Safrole      Congealing Point °C
   100               11.0
    90                7.5
    80                4.6
    70                1.7
    60               -1.3

(ex: Planta Medica.  61(6):574-575, 1995 Dec.ISSN 0032-0943)

Abstract: The root bark of Sassafras albidum (Nuttall) Nees Lauraceae) was
extracted at room temperature with hexane and chloroform as solvents. The
isolated essential oils were analyzed with GC and GC/MS. Thirty compounds
were identified, nine of which have not been previously reported from this
species. The major compounds were safrole (85%), camphor (3.25%), and
methyleugenol (1.10%). Ten sesquiterpenes were also identified.

------------------------------------------------------------------------------
AUSTRALIAN NATIVE TREE SPECIES BEARING SAFROLE
From the file: NATIVSAF.DOC
Cont: List of Australian native trees alleged to contain safrole.
Descriptions are supplied to assist recognition.

------------------------------------------------------------------------------
Page: 52  Fig: N/A  Ref:16
Species: Eremophila longifolia
Family: Myoporaceae
Synonyms: Stenochilus longifolius
Vernacular names: `Berrigan', `Emu bush', `Dogwood'.
Appearance: Tall erect shrub, up to 6m high, drooping branches.
            Finely hairy youngish shoots give it a grey appearance.
            Alternate leaves, 5-17cm long, narrow and tapered at both ends.
            Purplish 2.5cm long flowers are externally hairy the flower lobe
            is longer than broad, flowers occur in groups of up to three.
            Fruit is ovoid or globular, fleshy, dark coloured with a single
            hard four-celled stone. Flowers nearly all year round.
Habitat:    Limestone soils, usually inland, continental Aust except extreme
            north.
Active con: Leaves contain an essential oil rich in safrole and
methyleugenol.

------------------------------------------------------------------------------
Page: 72 Fig: N/A Ref:21
Species: Zieria Smithii
Family: Rutaceae
Synonyms: None
Vernacular names: Sandfly Zieria, Sandfly Bush, Lanoline Bush, `Stinkwood'
Appearance: A small to tallish shrub with opposite leaves. Each leaf
consists
            of three nearly hairless leaflets which vary from narrow to
            broadly egg-shaped, and are tapered at both ends, 2.5-5cm long.
            When crushed they exhibit a strong odour. Small 4-petalled white
            flowers occur in loose clusters in the forks of leaves in
Spring.
Habitat:    Common in sandy forest or cleared areas along the east coast
from
            Victoria to Northern Queensland.
Active Con: Foliage essential oil. Safrole, elemicin and methyleugenol may
            be present in major amounts in the steam-distilled oil.

------------------------------------------------------------------------------
Page: 80 Fig: N/A Ref: 16
Species: Atherosperma moschatum
Family: Atherospermae (Maybe Monimiaceae)
Synonyms: None
Vernacular names: Sassafras (Native, Black, Victorian, Southern)
Appearance: Small to medium tree, aromatic in all its parts. Young branches,
            flowers and the underside of the leaves are brownish or greyish
            hairy. Its opposite leaves are rigid and tapered at both ends,
            sometimes with toothed margins. Leaves are often arranged in one
            plane, length from 3-10cm. Solitary summer flowers in leaf
forks.
Habitat:    In rainforest and moist gullies of Tas, Vic and N.S.W. as far
            north as the Barrington Tops district.
Active Con: The bark oil probably contains safrole. Also numerous alkaloids.
Author notes: This species can be found with effort near the Upper Causeway
at
              Royal National Park, and also on the scree slopes of Wombarra,
              north of Wollongong, around the remains of the coal mine
              workings and impending drainage works.
Distillation: The leaves yield no safrole when dried, chopped finely and
              steam distilled, and only a miniscule amount of ti-tree
              (Maleleuca tree) - like oil.

------------------------------------------------------------------------------
Page: 83 Fig: N/A Ref: 71

Species: Cinnamomum laubatii
Family: Lauraceae
Synonyms: Cinnamomum tamala
Vernacular names: Camphorwood, Pepperberry, Pepperwood, Brown Beech.
Appearance: A tree up to 35m high with a straight, somewhat buttressed trunk
            and a smooth light brown bark, sometimes scaly on large trees.
            Freshly cut bark has a pleasant aroma. Young shoots and
            branchlets may be finely hairy. Leaves mostly opposite, oblong
            and tapered at both ends. 7.5-15cm long, showing three prominent
            ribs. Bunches of white flowers occur in upper leaf forks.
Habitat:    Coastal rainforests of northern Queensland.
Active con: The bark oil contains safrole, and some alkaloids.

------------------------------------------------------------------------------
Page: 85 Fig: N/A Ref: 13, 16

Species: Doryphora aromatica
Family: Atherospermataceae
Synonyms: Daphnandra aromatica
Vernacular names: Sassafras (Grey, Northern Grey, Net Sassafras, Cheedingnan
                  (Barron river)).
Appearance: A tree up to 35m high exhibiting large pustules, up to 6mm
across.
            Both the yellow wood and the bark are very aromatic. Young
            branchlets are sometimes 4-angled. Young shoots and flowers are
            hairy. Leaves are opposite, elliptical, tapered at both ends,
            6-15cm long and have toothed margins. Flowers are borne in the
            upper leaf forks at the end of the branchlets.
            Fruits are club-shaped or tubular, 1.5-2.5cm long. they split
            lengthwise when mature and release several tufted seeds. Differs
            from Daphnandra micrantha by being more
            aromatic and having less-toothed leaves as well as a larger
plume
            of hairs on the seed.
Habitat:    In the rainforests of northern Queensland.
Active con: The bark oil contains a volatile oil rich in safrole,
            plus several alkaloids.

------------------------------------------------------------------------------
Page: 86 Fig: N/A Ref: 16
Species: Doryphora sassafras
Family: Atherospermataceae
Synonyms: none
Vernacular names: Sassafras (NSW, caalang (Illawarra), boobin (North NSW),
                  tdjuendegong (Brisbane Water)).
Appearance: A large tree 20-30m high, exceptionally 40m. Opposite leaves are
            dark green and glossy, with coarsely toothed edges showing
            prominent veins on the underside. They are eliptical, tapered
            at both ends, narrowed at the base and 4-10cm long. Young shoots
            are silky hairy. Its short-stalked, starlike flower (usually
            three together) are pure white and occur in leaf forks, forming
            a stark contrast to the dark shining foliage. Flowers in early
            spring.
Habitat:    In the rainforests of the eastern districts of NSW and south
            Queensland. It occurs in the blue mountains west of Sydney and
            as far west as the Jenolan caves.
Active con: The leaves contains an essential oil rich in safrole, plus
            several alkaloids.

------------------------------------------------------------------------------
Page: 151 Fig: N/A Ref: 107, 108
Species: Cinnamomum oliveri
Family: Lauraceae
Synonyms: none
Vernacular names: Sassafras (Oliver's, camphorwood).
Appearance: A tall tree up to 45m high, with a brown, nodular bark, very
            fragrant when cut. Its opposite leaves are narrow and tapered
            at both ends, glossy above and much paler below, 20cm long and
            3.5cm broad. Velvety, cream coloured flowers occur in bunches
            15-20cm long in upper leaf forks or at then end of branchlets.
            Fruits are oval berries, 12mm long, containing a single seed,
            sometimes irregular in shape owing to numerous galls. Flowers in
            late spring to early summer. The similar Beilschmiedia
            obtusifolata has much broader leaves.
Habitat:    In the rainforests of northern NSW and southern Queensland.
Active con: The bark contains an essential oil rich in safrole, plus
            several alkaloids along with camphor, methyleugenol, or
            eugenol depending on the species.
It is not certain that the Australian authorities would go on an
enviropogrom
in order to destroy these plants. They have attempted to suppress marijuana
with only limited success. It is unlikely therefore that they can
successfully
suppress sassafras trees. Incidentally, yes you can find large stands of
sassafras trees near a town called Sassafras, NSW.

-----------------------------------------------------------------------------
2)                            S A F R O L E

-----------------------------------------------------------------------------
CAS numbers: Safrole [94-59-7]
Related CAS numbers: dihydrosafrole [94-58-6]
                     1'-hydroxysafrole [5208-87-7]
                     isosafrole [120-58-1]
Merck Index entry: 12th edition #8468
Beilstein entry: p 553 of _19_, 1 ,V.
Beilstein Database Registry Number: 136380.

---Synonymi---
1,2-methylenedioxy-4-allylbenzene        3,4-methylenedioxyallylbenzene
5-(2-propenyl)-1,3-benzodioxole          4-allyl-1,2-methylenedioxybenzene
allylchatecol methylene ether            allyldioxybenzene methylene ether
m-allylpyrocatechin methylene ether      allylpyrocatecholmethylene ether
1-allyl-3,4-methylenedioxybenzene

Safrole is also informally known as shikimole, by some bizarre phonetic
allusion to shikimic acid, a biological precursor to several aromatic
compounds, but which is chemically quite distant to safrole. The Japanese
name for Illicium religiosum Sieb et. Zucc is "Shikimi"

Some Physical Properties
------------------------
Chemical class:  aromatic bicyclic phenol ether
Solubility    :  insoluble in water
                 very soluble in ethanol, chloroform, diethyl ether
                 volatile with steam
Habit         :  Colourless or a reddish yellow liquid at room temp.
                 Solidifies into monoclinic prisms

Molar absorption     Peak Wavelength   Absorbance ( )
co-efficients at         236nm            4168.6
peak absorbance          285nm            3801.9
frequencies:

Molar Heat of
vapourisation : 13.2255kCal/gram mole

Heat of
combustion    :  1244.1 cal/kg

Diamagnetic
susceptibility:

Melting pt    :  11.2 °C
              :  Crude isolates are reported to melt at 7-8°C.

Boiling pts   :    231.5 °C at 760 mmHg (101.3kPa, atmospheric pressure)
                   233   °C at 759 mmHg
               100-101.5 °C at  11 mmHg
                    91   °C at   4 mmHg

Flash point   :  97°C
Optic Rotation:  nD(20) 1.5383
Density       :  1.096 g/cc at 20°C
Mol Wt        :  162.18g/mol
Empirical
formula       :  C10H10O2
Structural
formula       :  CH2:CHCH2C6H3O2CH2

Smell
---------------------
Safrole's smell has been variously described in terms of other molecules.
Safrole probably interacts with the same olfactory G-coupled receptors as
the volatiles in the anise plant, and this makes sense insofar as some of
the components in the oil of anise are structurally similar to safrole.
It is accurately described as a candy-shop odour. Go into a place which
sells
more sugary things than chocolatey things and take a deep whiff. It is also
reminiscent of ginger. It has been described as smelling like MDMA, anise,
rootbeer, sassafras oil, MDA, mCPP or sodium lactate. Halo-derivatives of
safrole are said to have similar smells to the parent molecule.
Safrole is conspicuously absent from the Sigma-Aldrich Flavours and
Fragrances
catalog. Some useful derivatives of safrole (piperonal "sweet, floral",
piperonyl acetate, "cherry, strawberry", piperonyl acetone and piperonyl
isobutyrate "fruity, berry") are present, however.

Structural diagrams
--------------------

        O  //\   /\           O  //\  /\\             O  //\   /CHO
       / \//  \ /  \         / \//  \/  \\           / \//  \ /
   H2C/   |   ||   ||    H2C/   |   ||   |       H2C/   |   ||
      \   |   ||   CH2      \   |   ||   CH3        \   |   ||
       \ /\\  /              \ /\\  /                \ /\\  /
        O  \\/                O  \\/                  O  \\/

       safrole             cis-isosafrole          piperonal (an aldehyde)

Toxicity
--------
LD50 in rats is 2.35g/kg.
It is mainly metabolised by the cytochromes P450.
Neither sassafras nor the oil should be taken internally. The use of herb
teas of sassafras may lead to a large dose of safrole. The use of safrole in
foods has been banned because of carcinogenic and hepatotoxic risks. The use
of safrole in toilet preparations is also controlled. A 47 year old woman
expeirnced `shakiness', vomiting, anxiety, tachycardia and raised blood
pressure following ingestion of a potentially fatal dose of sassafras oil
(5mL). Treatment was symptomatic following the use of activated charcoal.
See: Grande GA, Dannewitz SR,
     Symptomatic Sassafras Oil Ingestion,
     Vet. Hum. Toxicol 1987 29 447
Recognized Carcinogen P65, Suspected Gastrointestinal or Liver Toxicant,
Kidney Toxicant, Neurotoxicant, Reproductive Toxicant.
More hazardous than most chemicals in 6 out of 7 ranking systems.
At least 8 covalent adducts are formed when calf thymus DNA is incubated
with safrole-2',3'-oxide,an oxygenated metabolite of safrole in vitro.
However, no corresponding adducts are formed with liver DNA when whole
animals are exposed to safrole 2',3'-oxide, or safrole itself.
Although safrole 2',3'-oxide is readily formed in vivo, and is sufficiently
reactive to covalently bind to DNA, it is probably not a factor in the in
vivo genotoxicity of safrole. Tox. Letters. 75(1-3):201-207, 1995 Jan.
ISSN 0378-4274

Approximated FTIR Spectrum
--------------------------
Print out and play dot-to-dot for higher resolution <grin>.

     `                   '                                 `;
       '                                           `'
                                                                 ;
                                       ;                        `
                                                           <-917
                              '                        `  <-933
                           `
                                    `           '<-1043

----+-----------+-------+-----+------+------+------+-----+----+--------------
    |           |       |     |      |      |      |     |    |
   3000        2000  1600   1400    1200  1100   1000    900  800  cm-1

-Applications-

Safrole was used for decades in perfumes and medicines until in the 1960's.
Its primary industrial application was conversion to isosafrole, a precursor
to a dye called heliotropin and vanillin, a flavour molecule.
In the 1990s it was listed, along with isosafrole, on the prohibited
import regulations list, due to its application as a precursor in the
synthesis of banned psychoactive methamphetamines.
It is still used in the preparation of the following pharmaceutical
products:
Humexinal, Inhalador Vicks, Linimento Klari, Linimento Walderr, Zam-Buk and
Vegebom du Dr Miot, though in small quantities. Piperonyl butoxide, which is
used as a synergist in aerosol pesticides, is probably synthesised from a
safrole-derived feedstock.

-----------------------------------------------------------------------------
3) Safrole extraction and refinement

-----------------------------------------------------------------------------

-Isolation Methods-

Soxhletting the root bark of cinnamomum camphora (camphor laurel), or
probably parts of other plants (see below) with distilled ethanol, or hexane
and chloroform, yields most of the available safrole, and is cheap and
effective. The solvents can be evaporated off or reclaimed by distillation.
Dealing with the impurities in the soxhlet extract is another matter.
Steam distillation from bulk plant material is also reported to work.

-Refinement methods from oil-

1) Cool the oil or the safrole-containing fraction of the oil, to at least
   -12°C. Safrole will crystallise.
2) Use fractional distillation, followed by cooling and crystallisation.
   Regarding the distillation of safrole in mixtures consult
   Brauer, Ber Schimmel & Co, Jubiläums-Ausgabe (1929), 153.

3) Where safrole may be contaminated by oily constituents in an essential
   oil as in red camphor oil, the method of Ikeda and Takeda (a) may be
   employed advantageously to determine the safrole by preparation of the
   addition product with mercuric acetate and sodium chloride in dilute
   acetone. The precipitate so formed should be filtered in a Gooch funnel
   and weighed, and used with a correction factor to define the percentage
of
   safrole in the sample.
   This complex hydroxychloride of safrole [C10H10O2(OH)HgCl] according to
   Tsukamoto (b) is readily decomposed to regenerate safrole either by
sodium
   sulfide and zinc in potassium hydroxide; or hydrochloric acid. The
   oxychloride melts at 141-142°C according to Fujita (c).
     a) See: J. Chem.  Soc. Japan 57 (1936) 565
             Chem Abstracts 30 (1936) 7497
             Chem Abstracts 37 (1943) 3882
     b) See: J. Pharm. Soc. Japan 50 (1930) 7
             Chem Abstracts 24 (1930) 1853
     c) See: J. Chem.  Soc. Japan 58 (1937) 1185
             Chem Abstracts 32 (1938) 3904

-----------------------------------------------------------------------------
4) Derivatives and characterisation

-----------------------------------------------------------------------------

Safrole will convert to allylpyrocatechol when heated with phosphoric acid.
Safrole is oxidised to piperonylic acid (mp 238°C) by the action of
potassium permanganate in aqueous acetone. Some piperonylacetic acid
(mp 87-88°C) is also produced.
Safrole is oxidised to piperonal (heliotropin, mp 38°C) by the action of
potassium dichromate and dilute sulfuric acid.
Safrole isomerises to isosafrole when heated with alkalis.
See also step (3) in isolation, above.

---------ISOSAFROLE----(120-58-1)---------

 Isosafrole is technically a member of the styrenes and polymerises under
the
 influence of acids. It is soluble in ethanol, ether, benzene and is
 steam-volatile. It shares safrole's empirical formula and molecular weight.
 Isosafrole exists in two isomeric forms, the cis- isomer and the more
 energetically favourable trans- isomer. Warming converts the cis- form to
 the trans- configuration. Isosafrole is not as widely distributed in
 nature as safrole. It is best purified via a picrate derivative, the trans-
 isomer of which has mp 74.75°C. The picrate cis- isomer melts at 68.5°C.
 Cis-isosafrole boils at 253°C at 760mmHg; 179.5°C at 100mmHg.
 Trans-isosafrole melts at 6.7-6.8°C and boils at 247-247°C.
 Trans-isosafrole has a density of 1.122g/cc.

-------Halo-adducts---------

Tribromosafrole dibromide,
("pentabromosafrole") is prepared by dissolving 0.41g of safrole in 3mL of
ethanol, and treatment with 2g bromine for eight minutes. Heat for 15
minutes on a water bath, then cool. Recrystallise the solid from 7mL of
benzene. Needles, m.p. 169-170°C.

The 2-bromo-product,
the propyl arm is substituted with Br at the 2 position, from reaction with
HBr, is in Beilstein on p228 of _19_, 3/4, I. This bromo material is
reported
to have a density between 1.5614 and 1.5640, with the following boiling
points for given pressures in mmHg:

   mmHg     bp
                                CH3CHBrCH2Ph-O\
   13       154-157 °C                      \O-CH2
    9       145     °C          C  H  O Br
    5       130-135 °C           10 11 2

 References for this 2-bromopropyl product include (from Beilstein)
 Orcutt, Bogert,   Am. Soc. 58 [1936] 2055;
 Liebermann et al, Am. Soc. 69 [1947] 1540;
 Sakakibira, J. Chem. Soc Japan Pure Chem. Sect 73, [1952] 235;
 C. A. 1953 10511.

Markownikov Br-product
Getting this Markownikov depends on the absence of peroxides in the
precursor materials, such peroxides can be sequestered out by the addition
of a small quantity of hydroquinone (used in photography) to the reaction.
The 2-iodo-equivalent of the above, C  H  O I is produced with HI under
DMSO.
                                     10 11 2

        O  //\  /\                O  //\  /\
       / \//  \/  \              / \//  \/  \ /Br,I
   H2C/   |   ||  ||         H2C/   |   ||   |
      \   |   ||   CH2          \   |   ||   CH3
       \ /\\  /                  \ /\\  /
        O  \\/                    O  \\/

       safrole  + HBr => bromosafrole
                  HI  => iodosafrole

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5) Non regulated commercial sources

-----------------------------------------------------------------------------

Not tested: your mileage may vary.
Why would you want a tonne of safrole? Why, for synthesis into piperonyl
butoxide for use in insecticidal preparations, or manufacture of dyes,
flavours, etc, of course, and you're too lazy to extract it from plants.
Oils to order include
Juniper (var. virginialis) Oil, Sassafras Oil,
Brown Oil of Camphor, Nutmeg Oil

7 Old Bailey St
Central
Hong Kong

Urlekram A/S
Klostermarken 20, DK-9550 Mariager
Denmark

Terapi Consult AS
Frysjavien 27
0883 Oslo
Norway

Luonnonruo Katukku
Adukiky
Kirvesmeihenkatu 10, 00810 Helsinki
Finland

Whitefoods Wholesale
Unit 2D, Kylemore Industrial Estate
Dublin 10, Republic Of Ireland

Marunaka KK
1-12-4 Ginza Chuo-ku
Tokyo Japan

Grace & Pearl Corp'n
6, Lane 97
Tung An St
Taipei
Taiwan

Orient Resources Company, 506 Lucky Commercial Centre,
103-109 Des Voeux Road West, Hong Kong.
Tel: +852 25172316 Fax: +852 25178741
------------------------------------------------------------------------
PRODUCT                     ORIGIN        SPECS        PACKING   PRICE/KG
------------------------------------------------------------------------
Nutmeg Oil                  Sri Lankan                 180/200kg   $16.90
Pepper Oil                  Sri Lankan                 10/25/40kg  $70.00
Sassafras                                 95% Safrole              $6.00
------------------------------------------------------------------------
Prices quoted are for reference only in US$ on fob basis valid on 1st
August, 1996. Please contact us for firm quotations. Shipments can be
made by sea/air, minimum order US$5000. Quantity discounts available.
E-mail Questions and comments to orient@orc.com.hk  1995-97

-----------------------------------------------------------------------------
6) -References-

-----------------------------------------------------------------------------
General:
  Australian Medicinal Plants E.V. Lassak and T McCarthy 1983 Methuen
Australia
  44 Waterloo Rd North Ryde NSW 2213 ISBN: 0454004389 Dewey: 581.6'34'0994
  Dictionary of Plant Toxins (Baxter) 1996 J.Wiley and sons. ISBN 0471951072
  CRC Handbook of Medicinal Herbs (Duke) CRC Press
  Volumes 1-6, "The essential oils / by Ernest Guenther" 1948-56
  Modern Methods of Plant Analysis : Essential Oils and Waxes
  Edited by H.F. Linskens and J. F. Jackson (1991) ISBN 0-387-51915-7 and
  3-540-51915-7 Springer-Verlag p153 Dewey Call No. is 581.19072/1c/(12) ).
**Australian native sources of safrole:
  R. Hegnauer, Chemotaxonomie der Pflanzen, Vol 6, Birkhauser Verlag, Basel
  (1969)
  S.L.Everist, Poisonous Plants of Australia, Angus and Robinson, Sydney
(1974)
  31: L.J.Webb, Australian Phytochemical Survey, Part 2, CSIRO Bulletin
#268;
  Government Printer, Melbourne (1952)
  71: T.G.H.Jones, F. Berry-Smith, Proceedings of the Royal Society of
  Queensland, 37, 89 (1928)
  107:J.Lauterer, Proceedings of the Royal Society of Queensland, 11, 20
     (1894/5)
  108:E.Gildemeister and F.Hoffmann, Die Aetherischen Oele, vol. 5
    Akademie Verlag, Berlin, (1959)
**Other sources of Safrole:
  J G Maia et al, 'New Sources of Natural Safrole' in Perfumer & Flavorist
  Vol 18, Issue 2 March/April, p 19-22 (1993)
  L Zhu, D Ding, B Lawrence,  'The Cinnamomum Species in China: Resources
for
  the Present and Future', Perfumer & Flavorist Vol 19, issue 4, p17 (1994)
**Safrole chemistry
  Merck Index entry: 12th edition #8468
  PIHKAL, Alexander Shulgin, Transform Press
  Beilstein entry: p 553 of _19_, 1 ,V.
  Perkin W. H,  J. Chem. Soc. 1927 (1663)
  Martindales Pharmacopoea (30th Edn) entry p1410.3 (sassafras oil)
  FTIR: Morrison & Boyd Organic Chem (3rd Edn) Page 814, Fig FFF: Safrole.

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Addition by "Indole":

Chenopodium ambrosioides var. anthelminticum (Wormseed) (flowering plant,  
                                                         % unknown)

(this one is an oil that is restricted in most countries,
apparantly due to it's high ascaridole (up to 80%) content)

These are additions to the species already mentioned:

Cananga odorata (add. var. macrophylla, other variety doesn't seem to have
safrole/isosafrole), also Cananga odorata appears to have safrole, never
seen info saying it had isosafrole...

Myristica fragrans  (volatile seed oil, 0.2-0.6
			  (my ref has reports up to 2%)
Myristica fragrans  add:(husk oil, >1%)

Also, you could probably change Illicium verum from  (Star Anise...
disputed) to (fruit, unknown) or (fruit, low%) as the same ref. I keep
mentioning has info on this one...although it is low...

here's the ref if you need it:

Sheppard-Hanger, Sylla. (1995) "The Aromatherapy Practitioner Reference
Manual" Atlantic Institute of Aromatherapy, Tampa (Florida)
----------------------------------------------------------------------------
Anonymous:

Just thought you might like to add some info onto your safrole FAQ sheet on 
your site. The Australian botanicals, southern sassafras and ziera smiithi 
have no safrole in their roots, bark, trunks or foliage. Southern sass has 
nothing worth mentioning whilst smiithi contains lots of methyl eugenol, 
which is where the confusion started  I believe, the text 'poisionous plants 
of Australia' is fraught with errors and as much of the info in the current 
Safrole FAQ is lifted directly from this hence the errors.
This will save readers much time I believe as I have wasted heaps of time 
collecting , seperating and steam distilling all the bits. The methyl 
eugenol's existence was confirmed through FTIR and NMR library matches so 
there is no doubt to the accuracy of this info. The only assumption I am 
making is that maybe safrole only seasonally appears in these species, as 
my samples were all collected in winter/spring.

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