Forensic Science International 216 (2012) 19–28

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Forensic Science International

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Original research paper

The analysis of substituted cathinones. Part 3. Synthesis and characterisation of

2,3-methylenedioxy substituted cathinones
Pierce Kavanagh a,*, John O’Brien b, John Fox c, Cora O’Donnell c, Rachel Christie c, John D. Power d,
Seán D. McDermott d
a
Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Science, St. James Hospital, Dublin 8, Ireland
b
School of Chemistry, Trinity College, Dublin 2, Ireland
c
Department of Chemical and Pharmaceutical Science, Dublin Institute of Technology, Kevin St., Dublin 8, Ireland
d
Forensic Science Laboratory, Garda HQ, Dublin 8, Ireland

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

Article history: The first synthesis of the 2,3-isomers of MDPV, butylone and methylone is reported. The isomers were
Received 20 June 2011 characterised by 1H and 13C NMR spectroscopy and compared to the corresponding 3,4-isomers. A GC
Received in revised form 19 July 2011 method is described which separates the 3,4- and the 2,3-isomers from each other. IR spectra of the 2,3-
Accepted 14 August 2011
isomers are also compared with the corresponding 3,4-isomers. Two seized drug samples were analysed
Available online 9 September 2011
by GCMS and the samples were found to contain the 3,4-isomers.
ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords:
Forensic
Methcathinone
Drug
2,3-Isomers
Synthesis
Analysis

1. Introduction unambiguously stated in the legislation and the chemical analysis

gives an unambiguous result. Some difficulties arise when only one
Analogs of methcathinone that possess the methylenedioxy isomeric form of a drug is listed in the legislation as being
ring substituent on the phenyl ring are widely available controlled. This opens the possibility of asking forensic scientists to
to purchase on the internet [1]. Their popularity is related prove that the seized sample contains the controlled substance and
to their structural similarity to the commonly abused drug not a closely related analog. This process has been explored relative
3,4-methylenedioxymethamphetamine (MDMA, ‘‘Ecstasy’’). to methylenedioxyamphetamines [5,6] where the authors synthe-
Amongst the most common methylenedioxy methcathinones sised the 2,3-isomers of a series of 3,4-substituted amphetamines
are 3,4-methylenedioxymethcathinone (methylone), bk-MBDB and compared the pairs of isomers. Differences in the spectro-
(butylone) and 3,4-methylenedioxypyrovalerone (MDPV). scopic and chromatographic properties allowed for routine
The chemical characterisation of these compounds has been differentiation of the isomers.
previously reported [2–4]. The legal status of these compounds can The same problem exists with 3,4-substituted cathinones. The
vary from country to country, however they are widely abused and legislation in Ireland specifically names the 3,4-isomers of
frequently encountered in seized drug samples. methylone, butylone and MDPV as being controlled substances
New analogs of controlled drugs are encountered on an ongoing with no mention of the 2,3-isomers. It is therefore necessary to
basis in forensic laboratories. Part of the duty of the forensic establish that the seized compound is in fact the 3,4-isomer. NMR
chemist is to determine if the seized sample is a controlled analysis should easily differentiate the pairs of isomers, however
substance under the legal system in the country in question. This few forensic laboratories have such instruments and, in the
may be a straightforward process if the seized substance is presence of adulterants, NMR spectra can be difficult to interpret.
The 2,3-isomers of methylone, butylone and MDPV are not
available commercially and no reference to their synthesis or
* Corresponding author. Tel.: +353 18962044. characterisation could be found in the literature. With this as the
E-mail address: pierce.kavanagh@gmail.com (P. Kavanagh). background we proceeded to synthesise the 2,3-isomers, to

0379-0738/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.forsciint.2011.08.011
[(Fig._1)TD$IG]
20 P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28

O 1-(1,3-Benzodioxol-5-yl)-2-(methylamino) butan-1-one hydrochloride (3,4-

O butylone hydrochloride) (2b), 1-(1,3-benzodioxol-5-yl)-2-(methylamino) pro-
O pan-1-one hydrochloride (3,4-methylone hydrochloride) (1b) and 1-(1,3-benzo-
O dioxol-5-yl)-2-(pyrrolidin-1-yl) pentan-1-one hydrochloride (3,4-MDPV
hydrochloride) (3b) were all obtained from LGC, London, UK.
HN O HN
2.2. Synthesis of compounds
1a 1b
2.2.1. 1-(1,3-Benzodioxol-4-yl)-2-(methylamino) butan-1-one hydrochloride (2,3-
butylone hydrochloride) (2a)
O O 2.2.1.1. 1-(1,3-Benzodioxol-4-yl) butan-1-one. Propyl magnesium chloride (2 M,
O 25 ml, 50 mmol) was added to solution of 1,3-benzodioxole-4-carbaldehyde
O (5.00 g, 33 mmol), in THF (30 ml). The mixture was stirred overnight at room
O temperature. Water was cautiously added (5 ml) and the mixture was extracted
with dichloromethane. Drying (magnesium sulphate) and removal of the
HN HN
solvent afforded 1-(1,3-benzodioxol-4-yl) butan-1-ol as a yellow oil (5.75 g,
O 30 mmol). This was dissolved in dichloromethane (100 ml). Pyridinium
2a chlorochromate (7.66 g, 36 mmol) and silica (15 g) were added and the mixture
2b was stirred for 3 h. This mixture was passed through a short column of flash
silica and the solvent was removed. Flash column chromatography (hexane/
O ethyl acetate, 95/5) afforded colourless crystals (3.12 g, 12 mmol, 62%): 1H NMR
O O (CDCl3) d 7.42 (1H, d, J = 8.0 Hz, H-60 ), 6.99 (1H, d, J = 8.0 Hz, H-40 ), 6.91 (1H, tr,
J = 8.0 Hz, H-50 ), 6.10 (2H, s, H-70 ), 2.95, (2H, tr, J = 7.4 Hz, H-2), 1.76 (2H, m, H-3)
O O and 1.02 (3H, tr, J = 7.4 Hz, H-4); 13C NMR (CDCl3) d 197.9, 148.5, 147.6, 121.4,
121.2, 120.3, 112.2, 101.4, 44.3, 17.3 and 13.8; EIMS m/z (%) 192 (30.9), 149
N (100.0), 121 (7.1), 91 (7.1) and 65 (29.5); HR-ESIMS found 215.0678 (theor. for
O N M+Na, C11H12O3Na, 215.0679); m.p. 52–54 8C.

2.2.1.2. 1-(1,3-Benzodioxol-4-yl)-2-(methylamino) butan-1-one hydrochloride. Bro-

3a 3b mine (0.54 ml, 14 mmol) was added to a solution of 1-(1,3-benzodioxol-4-yl)
butan-1-one (2.00 g, 14 mmol) in dichloromethane (12 ml) and the mixture was
Fig. 1. Structures of 2,3- and 3,4-substituted cathinones. stirred for 2 h. The solvent was removed and methylamine solution in THF (20 ml,
2 M, 40 mmol) added. Flash chromatography (ethyl acetate/methanol, 99/1),
formation of the hydrochloride salt with ethereal hydrogen chloride (2 M) and
recrystallization from ethanol/acetone afforded a white powder (1.44 g, 7 mmol,
46%); 1H and 13C NMR (see Tables 3 and 4); EIMS m/z (%) 192 (3.5), 149 (6.1), 121
(2.6), 91 (2.2), 72 (100.0), 65 (5.2), 57 (5.3), and 42 (2.6); HR-ESIMS found 222.1128
characterise and compare them with the corresponding 3,4-
(theor. for M+H, C12H16O3N, 222.1125); m.p. 208–210 8C.
isomers.

2. Materials and methods 2.2.2. 1-(1,3-Benzodioxol-4-yl)-2-(methylamino) propan-1-one hydrochloride (2,3-

methylone hydrochloride) (1a)
2.1. Reagents and standards This was prepared as for 2,3-butylone using ethyl magnesium chloride (3 m in
diethyl ether) in the Grignard reaction.
1,3-Benzodioxole-4-carbaldehyde (2,3-methylenedioxybenzaldehyde) (May-
bridge Chemicals), hydrogen chloride (2 M) solution in diethyl ether (Acros
Organics), ethyl acetate (99.5% HPLC grade), hexane (95% HPLC grade), 2.2.2.1. 1-(1,3-Benzodioxol-4-yl) propan-1-one. 1-(1,3-Benzodioxol-4-yl) propan-1-
dichloromethane (99.8+% HPLC grade), acetone (99.8% HPLC grade) and one (2.72 g, 11 mmol, 54%), colourless crystals: 1H NMR (CDCl3) d 7.44 (1H, d,
pyridinium chlorochromate (Acros Organics) were purchased from Fisher J = 7.9 Hz, H-60 ), 7.00 (1H, d, J = 7.9 Hz, H-40 ), 6.91 (1H, tr, J = 7.9 Hz, H-50 ), 6.10
Scientific (Dublin, Ireland), butyl magnesium chloride (2 M in THF), piperonal, (2H, s, H-70 ), 3.00 (2H, q, J = 7.1 Hz, H-2) and 1.21 (3H, tr, J = 7.1 Hz, H-3); 13C
methylamine (2 M in THF), propyl magnesium chloride (2 M in diethyl ether), NMR (CDCl3) d 198.4, 148.5, 147.7, 121.5, 121.2, 120.1, 112.2, 101.4, 35.7 and
ethyl magnesium chloride (3 M in diethyl ether) anhydrous THF, bromine, 7.9; EIMS m/z (%) 178 (41.9), 149 (100.0), 121 (7.6), 91 (9.5) and 65 (35.7);
magnesium sulphate and pyrrolidine were purchased from Sigma Aldrich HR-ESIMS found 201.0524 (theor. for M+Na, C10H10O3Na, 201.0522); m.p. 47–
(Arklow, Ireland). 49 8C.

[(Fig._2)TD$IG]

Fig. 2. Gas chromatograph of 2,3- and 3,4-substituted cathinones.

[(Fig._3)TD$IG] P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28 21

Abundance
1100000 58 Scan 2068 (13.341 min): 8dc8321.D\data.ms

1000000

900000

800000

700000

600000

500000

400000

300000

200000

100000 149
42 91 121
50 66 77 107 135 164 178 192 207
0
40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210
m/z-->
2,3-Methylone (1a)

Abundance
850000 58 Scan 2123 (13.661 min): 8dc8321.D\data.ms

800000

750000

700000

650000

600000

550000

500000

450000

400000

350000

300000

250000

200000

150000

100000

121 149
50000
42 91
50 6 6 7 4 81 103 135 1 6 2 176 192 207
0
m/z--> 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210

3,4-Methylone (1b)

Fig. 3. Mass spectra of 2,3-methylone and 3,4-methylone.

2.2.2.2. 1-(1,3-Benzodioxol-4-yl)-2-(methylamino) propan-1-one hydrochloride. 1- 101.4, 42.1, 26.2, 22.4, and 13.9; EIMS m/z (%) 206 (17.6), 164 (63.8), 149 (100.0),
(1,3-Benzodioxol-4-yl)-2-(methylamino) propan-1-one hydrochloride (0.745 g, 121 (7.1), 91 (9.1) and 65 (30.0); HR-ESIMS found 229.0845 (theor. for M+Na,
4 mmol, 27% from the ketone intermediate), colourless crystals; 1H and 13C NMR C12H14O3Na, 229.0835).
(see Tables 1 and 2); EIMS m/z (%) 149 (7.8), 121 (5.2), 91 (3.5), 65 (8.7), 58 (100.0)
and 42 (3.0); HR-ESIMS found 208.0983 (theor. for M+H, C11H14O3N, 208.0968);
2.2.3.2. 1-(1,3-Benzodioxol-4-yl)-2-(pyrrolidin-1-yl) pentan-1-one hydrochloride. 1-
m.p. 206–208 8C.
(1,3-Benzodioxol-4-yl)-2-(pyrrolidin-1-yl) pentan-1-one hydrochloride (1.59 g,
5 mmol, 41% from the ketone intermediate), colourless crystals: 1H and 13C NMR
2.2.3. 1-(1,3-Benzodioxol-4-yl)-2-(pyrrolidin-1-yl) pentan-1-one hydrochloride (2,3- (see Tables 5 and 6) EIMS m/z (%) 232 (0.9), 204 (2.6), 149 (6.1) and 126 (100.0);
MDPV hydrochloride) (3a) HR-ESIMS found 276.1598, theor. for M+H, C16H22O3N, 276.1594); m.p. 174–
This was prepared as for 2,3-butylone using butyl magnesium chloride in the 176 8C.
Grignard reaction and using 2 M pyrrolidine in THF for the amination.

2.3. Sample analysis

2.2.3.1. 1-(1,3-Benzodioxol-4-yl) pentan-1-one. 1-(1,3-Benzodioxol-4-yl) pentan-1-
one (3.86 g, 18 mmol, 74%), colourless oil: 1H NMR (CDCl3) d 7.42 (1H, d, J = 8.0 Hz, 2.3.1. GCMS
H-60 ), 7.00 (1H, d, J = 8.0 Hz, H-40 ), 6.91 (1H, tr, J = 8.0 Hz, H-50 ), 6.10 (2H, s, H-70 ), Each of the samples, 1a–3b, was prepared by dissolving approximately
2.97 (2H, tr, J = 7.4 Hz, H-2), 1.73 (2H, m, H-3), 1.41 (2H, m, H-4) and 0.97 (3H, tr, 1 mg of each in 1 ml of methanol. A mixture of the six compounds was also
J = 7.4 Hz, H-5); 13C NMR (CDCl3) d 198.1, 148.5, 147.6, 121.4, 121.3, 120.3, 112.2, prepared by dissolving approximately 1 mg of each in 1 ml of methanol.
[(Fig._4)TD$IG]
22 P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28

Abundance
Scan 2152 (13.830 min)
: 8dc8321.D\data.ms
850000 72

800000

750000

700000

650000

600000

550000

500000

450000

400000

350000

300000

250000

200000

150000

100000

50000 57 149
42 121
91 135 164 192
81 107 177 221 205
0
m/z--> 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220
2,3-Butylone (2a)

Abundance Scan 2209 (14.162 min) : 8dc8321.D\data.ms

72
600000

550000

500000

450000

400000

350000

300000

250000

200000

150000

100000

50000 5 7 1 4 9
121
42 91
81 103 135 162 177 192 205 221
0
m/z--> 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220
3,4-Butylone (2b)

Fig. 4. Mass spectra of 2,3-butylone and 3,4-butylone.

Approximately 1 mg of each of the seized samples were dissolved separately in (400.13 MHz 1H and 100.6 MHz 13C). Proton NMR spectra are referenced to an
methanol. external TMS reference set at 0.00 ppm, coupling constants (J) are in Hertz (Hz)
All samples were injected directly onto an Agilent 6890N GC fitted with a 5975 High resolution electrospray mass spectra (HR-ESIMS) were recorded on by
Mass Selective Detector. The samples were run on a HP-ULTRA 1 capillary column direct injection on an LTQ Orbitrap Discovery (Thermo Fisher, UK). Melting points
(12 m  0.2 mm  0.33 mm) with helium carrier gas at a constant flow of 1 ml/min are uncorrected.
and a split ratio of 50:1. The injector was heated to 250 8C and the transfer line was
heated to 280 8C. Initial oven temperature is 80 8C, held for 1 min then ramped at
158/min to 110 8C and a hold time of 8 min, then ramped at 258/min to 295 8C and a
final time of 1 min. The total run time was 19.4 min. The mass spectra were
3. Results and discussion
collected after a 1.2 min solvent delay time. The collision energy was 70 eV and the
mass range was 40–450 m/z. The structures of the 3 pairs of isomers are shown in Fig. 1. The
synthesis of the 2,3-isomers is relatively straightforward and does
2.3.2. IR not pose a major synthetic challenge once the appropriate starting
IR spectra were run by preparing KBr discs of the samples. A Nicolet 380 FTIR
instrument was used and spectra were obtained using 32 scans with a resolution of
material (2,3-methylenedioxybenzaldehyde) is available. The avail-
4 cm1. The infrared spectrum was collected from 4000 to 400 cm1. ability of this starting material could be a problem however and
there is big price difference between this and the equivalent starting
2.3.3. NMR material for the 3,4-isomers, piperonal (3,4-methylenedioxyben-
Samples were prepared CDCl3 or DMSO-d6 and run on a Bruker Avance II 600 zaldehyde). The apparent absence of the 2,3-isomers on the
NMR (600.13 MHz 1H and 150.6 MHz 13C) or Bruker Avance III 400 NMR at clandestine market may be as much due to the pharmacological
[(Fig._5)TD$IG] P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28 23

Abundance Scan 2470 (15.684 min): 8dc8321.D\data.ms

126
2000000

1800000

1600000

1400000

1200000

1000000

800000

600000

400000

200000
65 84 96 149
42 54 110 164 177 246 204 216 232 258 273
0 137 188

m/z--> 40 60 80 100 120 140 160 180 200 220 240 260 280

2,3-MDPV (3a)

Abundance Scan 2514 (15.940 min): 8dc8321.D\data.ms

126
1800000

1600000

1400000

1200000

1000000

800000

600000

400000

200000
65 84 96 149
42 54 110 204 232
137 164 177 189 246 216 258 237
0
m/z--> 40 60 80 100 120 140 160 180 200 220 240 260 280

3,4-MDPV (3b)

Fig. 5. Mass spectra of 2,3-MDPV and 3,4-MDPV.

Table 1
NMR data for 2,3-methylone (1a).[TD$INLE]

3 Table 2
NMR data for 3,4-methylone (1b).[TD$INLE]

O H
2 N
1 2'
2' 1' 3'
O 1" 1
6' 1' 2 1"
7' 7'
6'
5' 4' 3
O 3' 5'
4'
13 1
Position 13
C (ppm) 1
H (ppm) Multiplicity J (Hz) Position C (ppm) H (ppm) Multiplicity J (Hz)

1 192.6 – – – 1 194.4 – – –
2 60.7 4.71 Quartet 7.1 2 58.0 5.12 Quartet 7.0
3 14.2 1.49 Doublet 7.1 3 15.8 1.45 Triplet 7.0
10 115.6 – – – 10 127.4 – – –
20 147.6 – – – 20 107.8 7.54 Doublet 2.0
30 148.5 – – – 30 148.3 – – –
40 113.8 7.28 Double doublet 8.0, 1.0 40 152.8 – – –
50 122.1 7.03 Triplet 8.0 50 108.6 7.16 Doublet 8.0
60 120.6 7.40 Double doublet 8.0, 1.0 60 125.8 7.72 Double doublet 8.0, 2.0
70 102.4 6.23 and 6.28 2 doublet Each 0.7 70 102.7 6.20 Singlet –
100 30.7 2.59 Singlet – 100 30.7 2.57 Singlet –
24 P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28

Table 3 Table 5
NMR data for 2,3-butylone (2a).[TD$INLE] NMR data for 2,3-MDPV (3a).[TD$INLE]

4 5

3 4
O 1" 3
2 N 4''
1 O
2' 1' 2 N
H 1 3''
O
6'
1'
7' O 2'
5' 6' 1" 2"
O 7'
3'
4'
5'
O 3'
Position 13
C (ppm) 1
H (ppm) Multiplicity J (Hz) 4'
1 192.1 – – –
2 65.2 4.78 Triplet 4.9 13 1
Position C (ppm) H (ppm) Multiplicity J (Hz)
3 21.5 1.98 and 2.10 2 multiplet –
4 8.1 0.85 Triplet 7.6 1 192.7 – – –
10 116.3 – – – 2 70.2 5.06 Multiplet –
20 147.7 – – – 3 30.6 2.00 Mutliplet –
30 148.0 – – – 4 16.8 1.10 and 1.36 2 multiplet –
40 113.8 7.29 Double doublet 8.0, 1.0 5 13.7 0.83 Triplet 7.3
50 122.1 7.04 Triplet 8.0 10 116.6 – – –
60 120.6 7.40 Double doublet 8.0, 1.0 20 148.2 – – –
70 102.4 6.23 and 6.28 2 doublet Each 0.7 30 148.8 – – –
100 31.4 2.57 Singlet – 40 114.0 7.30 Double doublet 8.0, 1.0
50 122.1 7.04 Triplet 8.0
60 120.6 7.40 Double doublet 8.0, 1.0
inactivity as to the synthetic challenge. It has been reported that 2,3- 70 102.4 6.23 and 6.30 2 doublet Each 0.6
100 51.7 3.27 and 3.57 2 multiplet –
MDA has only one fifth the CNS stimulant activity of 3,4-MDA [7].
200 22.77 2.04 and 1.93 2 multiplet –
The GCMS results for the individual isomers showed them to 300 22.75 1.98 and 1.95 2 multiplet –
have distinct retention times and to be isomerically pure. GC 400 54.0 3.52 and 3.10 2 multiplet –
results for a mixture of 1a–3b are shown in Fig. 2. The HP-ULTRA 1
column has a non-polar stationary phase and it can be seen that
these compounds can be separated using the conditions outlined
earlier. The elution order was established by injecting samples of
the individual isomers separately. The elution order for all three
Table 6
pairs of isomers is the 2,3-isomer followed by the 3,4-isomer. This NMR data for 3,4-MDPV (3b).[TD$INLE]
order is consistent with previous studies on the comparison

Table 4 2' 2"

NMR data for 3,4-butylone (2b).[TD$INLE] 3'
1
1' 2 1"
2' 7' 3
3' 6'
4'
1 4
1' 2 1" 5'
7'
6' 3 5
4'
4
5' Position 13
C (ppm) 1
H (ppm) Multiplicity J (Hz)

1 194.5 – – –
Position 13
C (ppm) 1
H (ppm) Multiplicity J (Hz) 2 67.0 5.41 Multiplet –
3 32.0 1.87–2.10 Multiplet –
1 193.9 – – – 200 22.8
2 62.4 5.18 Triplet 5.2 4 17.4 1.06 and 1.21 2 multiplet –
3 23.0 1.89 and 1.99 2 multiplet – 5 13.7 0.81 Triplet 7.3
4 8.2 0.77 Triplet 7.5 10 129.0 – – –
10 128.4 – – – 20 107.8 7.58 Doublet 2.0
20 107.8 7.15 Doublet 2.0 30 148.3 – – –
30 148.2 – – – 40 153.1 – – –
40 152.8 – – – 50 108.6 7.19 Doublet 8.0
50 108.5 7.57 Doublet 8.0 60 126.2 7.78 Double doublet 8.0, 2.0
60 125.8 7.74 Double doublet 8.0, 2.0 70 102.6 6.21 Singlet –
70 6.20 6.20 Singlet – 100 53.7, 51.9 3.00, 3.19, 4 multiplet –
100 31.3 2.54 Singlet – 3.45, 3.61
[(Fig._6)TD$IG] P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28 25

Fig. 6. Expanded 1H NMR of aromatic region of 2,3-methylone and 3,4-methylone.

[(Fig._7)TD$IG]

Fig. 7. IR of 2,3-methylone and 3,4-methylone.

[(Fig._8)TD$IG]
26 P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28

Fig. 8. IR of 2,3-butylone and 3,4-butylone.

between such isomers of various methylenedioxyamphetamines split), 50 as a doublet (ortho split) and 60 as a doublet of doublets
[5,6] and methylenedioxy butanamines/propanamines [8]. Addi- (ortho/meta split). The 1H NMR of 2,3-substituted aromatic
tionally, when the ring substitution pattern is kept constant (i.e. compounds similarly have characteristic patterns with 40 appear-
2,3- or 3,4-) the elution order is dictated by the size of the side ing as a doublet of doublets (ortho/meta split), 50 as an apparent
chain substituent, methylone < butylone < MDPV. This side chain triplet (di-ortho) and 60 as a doublet of doublets (ortho/meta split).
order was as expected and was the same order encountered in An expanded 1H NMR of the aromatic region of both methylone
earlier studies [5,6,8]. The mass spectra for the compounds are isomers is shown in Fig. 6. It is clear that NMR can be used to
presented in Figs. 3–5. There are no obvious differences in the distinguish between the respective isomers in this study.
spectra of the pairs of isomers. Mass spectrometry has been used to The IR spectra are shown in Figs. 7–9. It is clear that the
distinguish between 2,3- and 3,4-isomers of MDA/MDMA [5,6]. respective pairs of isomers can be differentiated from each other
Another study [8] stated that using conventional EI mass based on their IR spectrum. In general, the out of plane C–H
spectrometry, the compounds under investigation showed very bending bands in the region of 675 – 900 cm1 are used to
similar spectra with a dominant immonium base peak and only a differentiate between substituted aromatic compounds, and it is
few minor peaks, making the differentiation of regioisomeric clear that the 2,3-isomers differ from their 3,4-counterparts in this
compounds by this method alone impossible. The authors in that region. The difference in spectra can be attributed to the presence
study used GC–MS–MS to differentiate the isomers. In our study of three adjacent free hydrogen atoms in the 2,3-isomers compared
mass spectra could not be relied on to distinguish between the to one free hydrogen atom and two adjacent free hydrogen atoms
respective pairs of isomers. in the 3,4-isomers. Other regions are worthy of comment also. The
The NMR results for the 6 compounds are presented in Tables carbonyl C5 5O stretching band is affected by electronic and steric
1–6. The NMR spectra of the 3,4-isomers of butylone, methylone effects. Both of these are factors when considering the difference in
and MDPV have been published [2–4]. structure of the two pairs of isomers. For butylone and methylone
The 1H NMR of 3,4-substituted aromatic compounds have the carbonyl C5 5O stretching band has moved to a higher frequency
characteristic patterns, with 20 as appearing as a doublet (meta in the 2,3-isomer compared to the 3,4-isomer. This is likely to be
[(Fig._9)TD$IG] P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28 27

Fig. 9. IR of 2,3-MDPV and 3,4-MDPV.

[(Fig._10)TD$IG]

Fig. 10. Gas chromatograph of seized drug sample.

[(Fig._1)TD$IG]
28 P. Kavanagh et al. / Forensic Science International 216 (2012) 19–28

[(Fig._12)TD$IG]
Fig. 11. Gas chromatograph of seized drug sample.

HN 4. Conclusion

This study represents the first synthesis of the 2,3-isomers of

O methylone, butylone and MDPV. NMR and IR analysis can easily
distinguish between the isomers. The mass spectra of the isomers
O O do not differ significantly and cannot be used to distinguish
between isomers. The retention times of the isomers are different
Fig. 12. Structure of iso-butylone. using the chromatographic conditions outlined and therefore GC is
shown to be an excellent technique for separating the isomer and
due to the methylenedioxy group in the 2,3-isomers causing the determining which is present in a seized drug sample. Two seized
carbonyl group to be slightly out of plane leading to a higher samples were analysed and as expected were found to contain
frequency. This phenomenon is not observed in the MDPV isomers, the 3,4-isomers of methylone, butylone and MDPV which are
however the presence of the pyrrolidine-ring further complicates controlled in Ireland.
the steric forces acting on the carbonyl C55O stretching band. This
steric effect on the carbonyl band was also seen in the IR spectra of References
the 2, 3, and 4-isomers of mephedrone [9]. The different steric effects
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view that this compound is iso-butylone (Fig. 12). The presence of of 2-, 3- and 4- methylmethcatinone, Forensic Sci. Int. (2011), doi:10.1016/
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the reaction of 1-(1,3-benzodioxol-5-yl)-2-bromobutan-1-one with isomeric ethoxyphenethylamines and methoxymethcathinones, Forensic Sci. Int.
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