Forensic Science International 248 (2015) 140–147

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Forensic Science International

journal homepage: www.elsevier.com/locate/forsciint

Organic impurity profiling of 3,4-methylenedioxymethamphetamine

(MDMA) synthesised from catechol
Erin Heather, Ronald Shimmon, Andrew M. McDonagh *
Centre for Forensic Science, University of Technology Sydney, Sydney, NSW 2007, Australia

A R T I C L E I N F O A B S T R A C T

Article history: This work examines the organic impurity profile of 3,4-methylenedioxymethamphetamine (MDMA)
Received 23 June 2014 that has been synthesised from catechol (1,2-dihydroxybenzene), a common chemical reagent available
Received in revised form 18 December 2014 in industrial quantities. The synthesis of MDMA from catechol proceeded via the common MDMA
Accepted 19 December 2014
precursor safrole. Methylenation of catechol yielded 1,3-benzodioxole, which was brominated and then
Available online 31 December 2014
reacted with magnesium allyl bromide to form safrole. Eight organic impurities were identified in the
synthetic safrole. Safrole was then converted to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using
Keywords:
two synthetic methods: Wacker oxidation (Route 1) and an isomerisation/peracid oxidation/acid
Illicit drugs
3,4-Methylendioxymethamphetamine
dehydration method (Route 2). MDMA was then synthesised by reductive amination of MDP2P. Thirteen
MDMA organic impurities were identified in MDMA synthesised via Route 1 and eleven organic impurities were
Safrole identified in MDMA synthesised via Route 2.
Chemical synthesis Overall, organic impurities in MDMA prepared from catechol indicated that synthetic safrole was
Chemical profiling used in the synthesis. The impurities also indicated which of the two synthetic routes was utilised.
ß 2015 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Catechol (Scheme 1) is a common chemical reagent that is

The active ingredient in the drug colloquially referred to as
‘ecstasy’ is the amphetamine-type stimulant 3,4-methylenediox-
ymethamphetamine (MDMA), Fig. 1. First patented as ‘methylsa-
frylamin’ in 1912 as a precursor for blood-clotting agents [1,2], the
recreational use of MDMA gained popularity during the mid-1980s
and it has since become a prevalent drug of choice [1,3]. MDMA is
an illicit substance in many jurisdictions around the world and is
under international control through its inclusion to the United
Nations Convention against Illicit Traffic in Narcotic Drugs and
Psychotropic Substances 1988.
There has been a significant amount of research into the organic
impurity profiles of MDMA synthesised from the most common
precursors: 3,4-methylenedioxyphenyl-2-propanone (MDP2P),
safrole, isosafrole and piperonal [3]. These precursors, however,
are controlled or regulated substances in many jurisdictions. The
use of uncontrolled precursors therefore offers clandestine
laboratory operators a strategy to reduce the risk associated with
detection.
* Corresponding author at: University of Technology Sydney, P.O. Box 123,
Broadway, NSW 2007, Australia. Tel.: +61 2 95141035.
E-mail address: andrew.mcdonagh@uts.edu.au (A.M. McDonagh).
synthesised on an industrial scale with applications in the
synthesis of fragrances, pesticides, drugs and dyes [4]. Diversion
of catechol into illicit activities is therefore highly feasible. Safrole,
a common starting material for MDMA production, is a natural
product obtained from sassafras oil and is also used for the
industrial production of fragrances, flavours and some insecticides
[5]. The synthesis of safrole from synthetic precursors, including
catechol, has been investigated as a means to reduce the reliance
upon variable natural sources [5,6]. Thus, with such precedent as
well as available literature, it is unsurprising that this route has
been reported for the synthesis of MDMA in literature readily
available to the clandestine laboratory operator [7].
The techniques and procedures for the synthesis of MDMA from
uncontrolled precursors, including catechol, are described in detail
in numerous freely available documents on the internet [7]. There is,
however, only limited information available regarding the organic
impurity profiles that arise when these synthetic routes are utilised
[8]. Organic impurities in MDMA can result from precursors,
intermediates or reaction by-products [3] and their identification
can therefore provide valuable information about synthetic methods
currently in use. Of course, adulterants are a further source of
impurities however these will not be addressed here.
This paper presents the results of organic impurity profiling of
MDMA synthesised from catechol via the reaction pathways

http://dx.doi.org/10.1016/j.forsciint.2014.12.021
0379-0738/ß 2015 Elsevier Ireland Ltd. All rights reserved.
 E. Heather et al. / Forensic Science International 248 (2015) 140–147
Fig. 1. Chemical structure of MDMA.
shown in Scheme 1. As the organic impurity profile is dependent
on synthetic route, the synthesis of MDP2P from safrole was
performed via the two most common methods used in clandestine
laboratories – Wacker oxidation of safrole (Route 1) and the
isomerisation of safrole and peracid oxidation and acid dehydra-
tion of isosafrole (Route 2) [3,9,10]. We show that the organic
impurity profile of MDMA synthesised from catechol can indicate if
synthetic safrole (from catechol) was used. Importantly, numerous
impurities arise from these methods that are not reported in the
significant amount of literature describing impurities in MDMA
synthesised from commercially available safrole [3,9–11].
2. Materials and methods
2.1. General experimental
Each reaction was performed at minimum in duplicate. Gas
chromatography–mass spectrometry (GC–MS) analysis was per-
formed using an Agilent 6890 Series Gas Chromatographic System
coupled to an Agilent 5973 Network Mass Selective Detector.
Samples were prepared using diethyl ether as solvent at a
concentration of 5–10 mg/mL. The column was a Zebron ZB-5ms
5% polysilarylene-95% (5%-phenyl-95%-dimethylpolysiloxane)
with a length of 30 m, diameter of 250 mm and a film thickness
of 0.25 mm. The front inlet was at a temperature of 250 8C and had
a split injection, with a 1.0 mL injection volume and a 50:1 split
ratio. The transfer line was at a temperature of 280 8C. Helium was
used as a carrier gas at a rate of 1.2 mL/min. The temperature
programme had an initial oven temperature of 50 8C for 2 min,
followed by a ramp of 10 8C/min until 290 8C where it was held for
4 min. The scan parameters enabled collection of a mass range of
45–450 amu with an abundance threshold of 100. The data were
analysed using MSD Chem Station software. Proton nuclear
magnetic resonance (1H NMR) spectroscopy was performed using
an Agilent Technologies 500 MHz NMR instrument. Samples were
dissolved in deuterated chloroform (CDCl3) and the solvent
residual chemical shift of 7.26 ppm was used as an internal
standard to calibrate the spectra. The 1H NMR spectra were
collected at 25 8C with the following acquisition parameters:
Scheme 1. Synthesis of MDMA from catechol. (i) CH2Cl2, NaOH. (ii) HBr, H2O2, CH3COOH. (iii) 1: Mg, DIBAH; 2: allyl bromide. (iv) p-benzoquinone, PdCl2. (v) KOH. (vi) 1: H2O2,
HCOOH; 2: H2SO4. vii CH3NO2, Al(Hg).
141
16 acquisitions, 8012.8 Hz spectral width, 4.089 s acquisition time,
1.0 s relaxation delay and 60.0 degree pulse. Spectra are available
in the supplementary data files.
2.2. Chemicals
Catechol, diisobutylaluminium hydride (DIBAH, 1.5 M solution
in cyclohexane), allyl bromide, magnesium, anhydrous tetrahy-
drofuran, p-benzoquinone, formic acid and nitromethane were
purchased from Sigma–Aldrich. Diethyl ether, dichloromethane,
methanol, acetone, toluene, hydrogen peroxide (30%), ammonium
chloride and sodium hydroxide were purchased from Chem-
Supply. Dimethyl sulfoxide, mercuric chloride and hydrobromic
acid (46–49%) were obtained from UNILAB. Glacial acetic acid,
hydrochloric acid (36%) and sodium bicarbonate were purchased
from Labscan. Sulphuric acid was purchased from BDH Chemicals.
Anhydrous sodium sulphate was purchased from AJAX Finechem.
Sodium bisulfite was obtained from the Mallinckrodt Chemical
Works. Chloroform-D was purchased from Cambridge Isotope
Laboratories, Inc.
2.3. Synthesis
Synthesis of 1,3-benzodioxole: Catechol (20.0 g, 182 mmol) and
an aqueous solution of sodium hydroxide (30 mL, 19.4 M,
582 mmol) were dissolved in 200 mL of dimethyl sulfoxide. The
resultant green solution was heated to 90–100 8C. Dichloro-
methane (40 mL, 626 mL) was added drop wise to the solution,
which was heated under reflux at 90–100 8C for 4 h. The mixture
was allowed to cool and 200 mL of water was added. The mixture
was decanted and the product was extracted with diethyl ether
(3 200 mL). The diethyl ether extracts were washed with 3
200 mL of water, dried over anhydrous sodium sulphate and
decanted. Solvent was removed with a rotary evaporator,
producing a light brown oil. Yield: 14.8 g (66.7%). 1H NMR: Fig.
S1. GC–MS: Fig. S9.
Synthesis of 5-bromo-1,3-benzodioxole: 1,3-Benzodioxole
(6.00 mL, 52.2 mmol) was dissolved in a mixture of glacial acetic
acid (2.6 mL, 45 mmol), 16 mL of methanol, and 2 mL of water.
Hydrobromic acid (6.0 mL, 8.9 M, 53 mmol) was then added
dropwise to the solution ensuring that the temperature remained
below 25 8C. The solution was heated to approximately 35 8C, and
hydrogen peroxide (6.0 mL, 9.9 M, 59 mmol) was added drop wise,
ensuring that the temperature did not exceed 50 8C. The resulting
solution was stirred at 40–50 8C for 3 h and allowed to cool. The red
organic layer was extracted with diethyl ether (1 40 mL) and
142 E. Heather et al. / Forensic Science International 248 (2015) 140–147
washed with 10 mL of aqueous 10% sodium bisulfite solution. The
ether extracts were dried over anhydrous sodium sulphate,
decanted and the solvent removed with a rotary evaporator,
producing an orange oil. Yield: 8.95 g (85.2%). 1H NMR: Fig. S2. GC–
MS: Fig. S10.
Synthesis of safrole: The following Grignard reaction was
conducted using dry glassware under nitrogen. Magnesium
(0.60 g, 25 mmol), 5-bromo-1,3-benzodioxole (0.40 mL, 3.3 mmol)
and a 1.5 M solution of DIBAH in cyclohexane (0.10 mL, 150 mmol)
were stirred in 20 mL of anhydrous THF. Additional 5-bromo-1,3-
benzodioxole (2.60 mL, 21.5 mmol) was added drop wise and the
mixture was stirred for 2 h. The solution was removed via syringe
and added dropwise to allyl bromide (4.0 mL, 46 mmol) contained
in an ice bath. The solution was stirred for 24 h and reaction
quenched by the addition of 20 mL of water and 20 mL of saturated
ammonium chloride. The product was extracted into 3 80 mL of
diethyl ether and washed with 3 100 mL of water. The ether
extracts were dried over anhydrous sodium sulphate, decanted,
and the solvent removed with a rotary evaporator, producing a
brown oil. Yield: 3.30 g (82.1%). 1H NMR: Fig. S3. GC–MS: Fig. 2.
Synthesis of MDP2P (Route 1): Safrole (1.00 g, 6.17 mmol) was
dissolved in 1 mL of methanol and added dropwise to a mixture of
palladium (II) chloride (12 mg, 68 mmol), p-benzoquinone (0.85 g,
7.9 mmol), 5 mL of methanol and 0.5 mL of water. The resulting
mixture was stirred for 3 h and filtered. To the filtrate, 10 mL of
3.2 M hydrochloric acid was added. The product was extracted
with 3 20 mL of dichloromethane and washed with 2 20 mL of a
saturated sodium bicarbonate solution, 2 20 mL of 1.3 M sodium
hydroxide and 2 20 mL of brine. The organic extracts were dried
over anhydrous sodium sulphate, decanted and the solvent
removed with a rotary evaporator, producing a brown oil. Yield:
857 mg (78.0%). 1H NMR: Fig. S4. GC–MS: Fig. S11.
Synthesis of isosafrole (Route 2): Safrole (1.40 g, 8.63 mmol) was
dissolved in a 3 M solution of potassium hydroxide in 1-butanol
(10 mL, 30 mmol). The resulting solution was heated under reflux
for 3 h and allowed to cool. To the solution, 10 mL of a 1.6 M
hydrochloric acid solution was added. The product was extracted
with 3 40 mL of diethyl ether and washed with 3 40 mL of
water. The organic extracts were dried over anhydrous sodium
sulphate, decanted, and the solvent removed with a rotary
evaporator, producing a brown oil. Yield: 1.19 g (85.0%). 1H
NMR: Fig. S5. GC–MS: Fig. S12.
50
45
40
35
30
Abundance (×105)
25
20
15
10
0
4 6 8 10
Fig. 2. Gas chromatogram of safrole synthesised from catechol.
Synthesis of MDP2P (Route 2): A solution containing hydrogen
peroxide (2.0 mL, 9.9 M, 20 mmol) and formic acid (10 mL, 23.6 M,
240 mol) was stirred at room temperature for 30 min. Isosafrole
(800 mg, 4.93 mmol) in 6 mL of acetone was added to the solution
and stirred at room temperature for 16 h. The volatile components
of the resulting solution were removed in vacuo, leaving a red
residue. The residue was redissolved in 10 mL of methanol and
10 mL of 2.8 M sulphuric acid was added. The resulting solution
was heated under reflux for 3 h and allowed to cool. The product
was extracted with 3 40 mL of diethyl ether and washed with
40 mL of water and 40 mL of saturated sodium bicarbonate
solution. The ether extracts were dried over anhydrous sodium
sulphate, decanted and the solvent removed with a rotary
evaporator, producing a brown oil. Yield: 538 mg (61.2%). 1H
NMR: Fig. S6. GC–MS: Fig. S13.
Synthesis of MDMA: Aluminium foil (280 mg, 10.4 mmol), cut in
approximate 1 cm  1 cm squares, was added to a solution of
mercuric chloride (80.0 mg, 295 mmol) in 10 mL of methanol. The
mixture was heated under reflux until the aluminium foil turned a
dark grey and bubbles formed on the surface. Then, a solution of
MDP2P (200 mg, 1.12 mmol) and nitromethane (0.20 mL,
3.7 mmol) in 5 mL of methanol was added [note: this procedure
was performed using MDP2P synthesised by Route 1 and also with
MDP2P synthesised by Route 2]. The resulting mixture was heated
under reflux for 4 h and allowed to cool. An 8.8 M sodium
hydroxide solution was added to the mixture until the majority of
amalgam had dissolved. The mixture was filtered and the product
extracted from the filtrate with toluene (3 20 mL). The solvent
was removed with a rotary evaporator, producing a light brown oil.
Yield: 136 mg (62.7%). 1H NMR: Figs. S7–S8. GC–MS: Figs. 3–4.
3. Results and discussion
The synthetic methods described here were chosen such that
they could be feasibly performed in a moderately equipped
clandestine laboratory. Elaborate product purification techniques
were not used so as to mimic the procedures that may be expected
in relatively unsophisticated clandestine laboratories. As such,
there were some variations in the concentration of organic
impurities that were detected across series of repeat synthesises.
The products from each step in the reaction pathway were
analysed using GC–MS and 1H NMR spectroscopy. Organic
12 14 16 18 20 22 24 26 28 30
Time (min)
 E. Heather et al. / Forensic Science International 248 (2015) 140–147 143

18

16

14

12

Abundance (×105) 10

0
4 6 8 10 12 14 16 18 20 22 24 26 28 30
Time (min)

Fig. 3. Gas chromatogram of MDMA synthesised from catechol via Route 1.

impurities were identified based on the fragmentation pattern of
their mass spectrum. The identification of these organic impurities
was also confirmed by 1H NMR spectroscopy when impurities were
of a sufficient concentration to produce distinct NMR signals.
3.1. Safrole from catechol
Safrole was synthesised from catechol in three steps: the
methylenation of catechol, the bromination of 1,3-benzodioxole
and a Grignard reaction using 5-bromo-1,3-benzodioxole and allyl
bromide. The gas chromatogram of safrole synthesised from
catechol is shown in Fig. 2 and the eight impurities identified
unambiguously are listed in Table 1.
Compounds 4, 5, and 8 arose during the methylenation of
catechol (Step 1, Scheme 1). Compound 4 was formed through the
cyclisation of two catechoxide dianions with dichloromethane
while compound 8 was synthesised via a similar reaction involving
the cyclisation of three catechoxide dianions with dichloro-
methane. The formation of compound 5 involves methylenation
across the aromatic rings of two 1,3-benzodioxole molecules.
Compounds 1 and 2 are intermediates in the synthesis of safrole
from catechol. Their presence indicates that the reactions ii–iii
(Scheme 1) did not proceed to completion. Compound 1, however,
is also a reaction by-product in the Grignard reaction (Step 3,
Scheme 1) whereby the Grignard reagent, formed through the
reaction of 5-bromo-1,3-benzodioxole and magnesium, reacts
with water to form 1,3-benzodioxole (1), as shown in Scheme 2.
This decomposition could occur due to water contamination in the
reactant setup or result from an incomplete reaction at the time
when the reaction mixture was quenched.
Compound 6 is also a reaction by-product of the Grignard
reaction, as shown in Scheme 2, arising from the reaction of the
Grignard reagent with 5-bromo-1,3-benzodioxole [12]. Com-
pounds 3 and 7 are synthesised by Grignard reactions of the
bromination reaction by-product, 5,6-dibromo-1,3-benzodioxole,
via the reaction schemes shown in Scheme 3.

25

20

15
Abundance (×105)

10

0
4 6 8 10 12 14 16 18 20 22 24 26 28 30
Time (min)

Fig. 4. Gas chromatogram of MDMA synthesised from catechol via Route 2.

144 E. Heather et al. / Forensic Science International 248 (2015) 140–147

Table 1
Organic impurities identified in safrole synthesised from catechol.

No. Impurity structure Impurity name m/z

1 1,3-Benzodioxole 122/121, 63

2 5-Bromo-1,3-benzodioxole 202/200, 121, 63

3 5-Bromo-6-(2-propenyl)-1,3-benzodioxole 242/240, 199, 131, 103, 77

4 1,3-Benzodioxole dimer 244, 135, 122/121, 63

5 5,50 -Methylenebis-1,3-benzodioxole 256, 135, 77

6 5,50 -Bi-1,3-benzodioxole 242, 126, 121/120, 63

7 5-Allyl-6-(1,3-benzodioxol-5-yl)-1,3-benzodioxole 282, 267, 237, 209, 165, 139

8 1,3-Benzodioxole trimer 366, 244, 135, 122/121

H2O

Scheme 2. Synthesis of 1,3-benzodioxole (1) and 5,50 -bi-1,3-benzodioxole (6).

Mg

2Br -

2Mg

Scheme 3. Synthesis of 5-bromo-6-(2-propenyl)-1,3-benzodioxole (3) and 5-allyl-6-(1,3-benzodioxol-5-yl)-1,3-benzodioxole (7).

 E. Heather et al. / Forensic Science International 248 (2015) 140–147 145

Table 2
Organic impurities identified in MDMA synthesised from catechol via Route 1 and Route 2.

No. Impurity structure Impurity name m/z Synthetic route

1 1,3-Benzodioxole 122/121, 63 1

2 5-Bromo-1,3-benzodioxole 202/200, 121, 63 1 and 2

4 1,3-Benzodioxole dimer 244, 135, 122/121, 63 1 and 2

5 5,50 -Methylenebis-1,3-benzodioxole 256, 135, 77 1 and 2

6 5,50 -Bi-1,3-benzodioxole 242, 126, 121/120, 63 1 and 2

8 1,3-Benzodioxole trimer 366, 244, 135, 122/121 1

10 cis and trans isosafrole 162, 131, 104/103, 77, 44 1

11 5-(1-Methoxypropyl)-1,3-benzodioxole 194, 165, 150/149, 135, 77 1

12 5-(1,3-Dimethoxypropyl)-1,3-benzodioxole 224, 192, 161, 135, 75 1

13 MDP2P dimethyl acetal 224, 193, 135, 89 1 and 2

14 5-(3,3-Dimethoxypropyl)-1,3-benzodioxole 224, 192, 161, 135, 75 1

15 1-[6-(1,3-Benzodioxol-5-yl)-1,3-benzodioxol-5-yl]-N- 256, 58, 44 1

methyl-propan-2-amine

16 1,3-Benzodioxole-5-carboxylic acid 166, 150/149, 135, 121, 77 2

146 E. Heather et al. / Forensic Science International 248 (2015) 140–147

Table 2 (Continued )

No. Impurity structure Impurity name m/z Synthetic route

17 MDP2P methyl hemiacetal 196, 165, 150/149, 135, 121, 63 2

18 1-(1,3-Benzodioxol-5-yl)-1-methoxy-propan-2-ol 210, 165, 150/149, 135, 77 2

19 2,4-Dimethyl-3,5-bis(3,4-methylenedioxyphenyl) 340, 296, 281, 207, 44 2

tetrahydrofuran

3.2. MDMA from safrole
MDMA was synthesised by reductive amination of MDP2P. Two
methods were used to synthesise MDP2P; Wacker oxidation of
safrole (Route 1) and an isomerisation/peracid oxidation/acid
dehydration method (Route 2). The gas chromatograms of MDMA
synthesised from catechol via Route 1 and Route 2 are shown in Fig. 3
and Fig. 4, respectively. The organic impurities identified in MDMA,
and the synthetic routes from which they arose, are listed in Table 2.
Compounds 1, 2, 4–6 and 8 found in MDMA synthesised via
Route 1 were identified as impurities in safrole (Table 1) and have
been carried over, unchanged, in subsequent reactions. Compound
15 arose from compound 7 (identified in safrole) via an analogue
route to MDMA, as shown in Scheme 4.
Compounds 2, 4, 5 and 6 were also identified in MDMA
synthesised via Route 2. Compounds 1, 8 and 5-(1,3-benzodioxol-
5-yl)-6-prop-1-enyl-1,3-benzodioxole (isomerisation product of
compound 7 identified in safrole) were found in isosafrole.
However, these impurities were not detected in MDP2P and
MDMA as they were removed during the peracid oxidation and
acid dehydration of isosafrole.
With the exception of 1,3-benzodioxole (1), compounds 2, 4–6
and 8 and 15 have not been previously identified in sassafras oil or
MDMA prepared from sassafras oil [11,13]. Furthermore, they have
not been identified in MDMA synthesised from commercially
available MDP2P, safrole, isosafrole and piperonal [3]. The
identification of compounds 2–6, 8 and 15 therefore indicates
the use of safrole, synthesised from catechol, as a precursor to
MDMA. Thus, elements of the organic impurity profile of MDMA
synthesised from catechol via both Route 1 and Route 2
unambiguously indicate the use of synthetic, catechol-derived
safrole (as discussed below).
Compounds 4, 5 and 8 are characteristic of the methylenation of
catechol; the detection of any of these impurities therefore
indicates that catechol was the precursor utilised. The presence of
compound 2 is indicative of the bromination reaction used in the
second step of the synthetic pathway. The Grignard reaction, used
in the final step of the synthesis of safrole, can be inferred by the
presence of compounds 6 and/or 15, which are characteristic
impurities formed when the Grignard reagent is prepared from
5-bromo-1,3-benzodioxole (2).
The synthesis of MDP2P from safrole via Route 1 or Route 2 can
also be differentiated based upon the organic impurity profile of
MDMA. Compounds 11, 12 and 14 are characteristic impurities for
the Wacker oxidation of safrole when methanol is used as a solvent
[10] and, therefore, their identification in MDMA is indicative of
synthesis via Route 1. Similarly, compounds 18 and 19 are
characteristic for the peracid oxidation and acid dehydration of
isosafrole [9] and their identification in MDMA is indicative
of synthesis via Route 2. There are two diasteroisomers identified

PdCl2 CH3NO 2
Al(Hg)

Scheme 4. Synthesis of 1-[6-(1,3-benzodioxol-5-yl)-1,3-benzodioxol-5-yl]-N-methyl-propan-2-amine (15).

[O] [O]

Scheme 5. Synthesis of 1,3-benzodioxole-5-carboxylic acid (16).

 E. Heather et al. / Forensic Science International 248 (2015) 140–147
of both compounds 18 and 19, however, the stereoconfiguration of
these cannot be determined without isolation of the impurity.
Isosafrole (10) is also a reaction by-product of the Wacker
oxidation of safrole that was synthesised via the palladium-
catalysed isomerisation of safrole. Compound 16 was synthesised
through the oxidation of isosafrole, as shown in Scheme 5, during
the peracid oxidation and acid dehydration of isosafrole. Isosafrole
can be detected in MDMA samples as a result of a reaction by-
product, an intermediate or a precursor in a synthetic route. The
identification of isosafrole, or impurities stemming from isosafrole,
in MDMA is therefore not indicative of a particular synthetic route.
Compounds 13 and 17 are by-products of the reductive amination
of MDP2P, synthesised through the reaction of MDP2P with the
reaction solvent, methanol [8]. The MDMA synthesised via Route 2
contains both of these impurities, whereas the MDMA synthesised
via Route 1 contains only impurity 13 in a significantly lower
concentration. This demonstrates that there can be large variation in
the organic impurity profiles of reaction products when synthesised
in a clandestine laboratory environment. In such an environment,
these variations could be introduced due to an imperfect reaction
setup, variations in reaction conditions or variations in the technique
of different chemists performing the reaction.
4. Conclusions
Safrole was synthesised from catechol, a common industrial
chemical, via a three-step synthetic pathway that could be feasibly
performed in a moderately equipped clandestine laboratory. The
synthesis involved the methylenation of catechol, the bromination
of 1,3-benzodixole and a Grignard reaction using 5-bromo-1,3-
benzodioxole and allyl bromide. Eight organic impurities were
identified in the synthetic safrole and, of these impurities, only one
(1,3-benzodioxole) has previously been identified in safrole
obtained from natural sassafras oil.
The synthesis of MDP2P from safrole was performed via two
common synthetic methods: Wacker oxidation (Route 1) and an
isomerisation/peracid oxidation/acid dehydration method (Route
2). MDMA was then synthesised by reductive amination of MDP2P
in both of these synthetic routes. Thirteen organic impurities were
identified in MDMA synthesised via Route 1 and eleven organic
impurities were identified in MDMA synthesised via Route 2.
147
The organic impurity profile of MDMA synthesised from
catechol via both Route 1 and Route 2 indicated that synthetic,
catechol-derived safrole was used. The organic impurities identi-
fied also indicated which of the two synthetic routes was utilised.
We conclude, therefore, that the organic impurities identified in
MDMA indicated the precursor and the reaction pathway used to
synthesise MDMA from catechol.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.forsciint.2014.12.021.
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