Journal of Chromatographic Science, Vol.

34, January 1996

Analysis of 1 - ( 3 - M e t h o x y - 4 , 5 - M e t h y l e n e d i o x y p h e n y l ) - 2 -

P r o p a n a m i n e ( M M D A ) Derivatives Synthesized f r o m N u t m e g

Oil a n d 3 - M e t h o x y - 4 , 5 - M e t h y l e n e d i o x y b e n z a l d e h y d e

C. Randall Clark* and Jack DeRuiter

D e p a r t m e n t of Pharmacal Sciences, School of P h a r m a c y , A u b u r n U n i v e r s i t y , A u b u r n , A l a b a m a 36849

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F. Taylor Noggle
A l a b a m a D e p a r t m e n t o f Forensic Sciences, W i r e R o a d , A u b u r n , A l a b a m a 36830

Abstract Based on these synthetic strategies, the availability of the

precursors and related substances has been controlled by the
Myristicin, a natural product found in nutmeg oil and nutmeg Drug Enforcement Administration under the Chemical Diver­
extract, contains the carbon skeleton for a series of drugs of abuse sion and Trafficking Act in March of 1989 (5). The restricted
related to the 3,4-methylenedioxyamphetamines ( M D A s ) . Myristicin, availability of these key precursors has prompted clandestine
1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propene, was identified laboratory operators to seek alternative approaches for the syn­
as the major component of commercially available nutmeg oil and in thesis of amphetamines and MDA-type compounds and to ex­
the organic extract of nutmeg powder. T h e starting materials, plore the synthesis of new, structurally related compounds or so-
intermediates, and products in the synthesis of the drug of abuse
called designer drugs for which precursor chemicals are
N-methyl-1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanamine
available. For example, an alternate method reported for the syn­
( M M D M A ) f r o m myristicin w e r e characterized by gas chromato-
graphic-mass spectrometric analysis. M M D M A and several primary
thesis of MDMA uses the natural product safrole (6), which is
amine derivatives including 1-(3-methoxy-4,5-methylene- commercially available or can be obtained by extraction or dis­
dioxyphenyl)-2-ethanamine, -propanamine, and -butanamine w e r e tillation of the sassafras plant, which is native to the United
also prepared f r o m the commercially available aldehyde, 3-methoxy- States. Safrole may be used to synthesize the ketone MDP-2-P or
4,5-methylenedioxybenzaldehyde. Each of these amine derivatives may be brominated with hydrobromic acid to yield l-(3,4-
has a distinct mass spectrum characterized by amine-dominated methylenedioxyphenyl)-2-bromopropane, which can be con­
fragmentation. A l l four amines in this study w e r e resolved by verted to MDMA by direct displacement with methylamine. This
reversed-phase liquid chromatography using an acidic aqueous same synthetic approach could be used with the primary com­
mobile phase. Relative retention in this system was determined by
ponent of nutmeg oil, myristicin, to yield l-(3-methoxy-4,5-
differences in the hydrophobic surface area of the four amines.
methylenedioxyphenyl)-2-propanamine derivatives such as the
N-methyl analogue MMDMA and the primary amine MMDA.
These compounds are the m-methoxy analogues of MDMA and
Introduction
A number of phenalkylamines (Chart 1) including the am­
phetamines (amphetamine and methamphetamine) and 3,4-
methylenedioxyamphetamines (MDA, MDMA) remain popular
drugs of abuse in the United States and abroad (1). These com­
pounds are synthesized in clandestine laboratories by a variety
of methods using commercially available synthetic precursors.
For example, methamphetamine is commonly prepared by
hydrogenolysis reactions using the ephedrines or pseu-
doephedrines or by reductive amination of 1-phenyl-2-
propanone (P-2-P) (2,3). Similarly, 3,4-methylenedioxymeth-
amphetamine is typically synthesized by reductive amination of
l-(3,4-methylenedioxyphenyl)-2-propanone (MDP-2-P) (4). The
synthetic route by which illicit samples of these compounds are
produced can frequently be determined by complete charac­
terization and analysis of the sample (2–4).
Chart 1. Synthetic drugs of abuse: amphetamine, methamphetamine,
MDA, MDMA, MMDA, and MMDMA.
* Author to whom correspondence should be addressed.

34 Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission.
Journal of Chromatographic Science, Vol. 34, January 1996

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Figure 1. Gas chromatographic-mass spectral analysis of nutmeg oil: A, chromatogram; B, mass spectrum of myristicin (1-(3-methoxy-4,5-methylenedioxyphenyl)-
2-propene). Peaks: 1, γ-terpinene (3.84 min); 2, α-terpinolene (4.13 min); 3, terpinen-4-ol (4.87 min); 4, safrole (5.60 min); and 5, myristicin (7.03 min).

Figure 2. Gas chromatographic analysis of a methanol extract of nutmeg spice. Peaks: 1, terpinen-4-ol (4.87 min); 2, safrole (5.64 min); 3,1-(3,4-dimethoxyphenyl)-
2-propene (6.28 min); 4, myristicin (7.02 min); 5,1-(3,4,5-trimethoxyphenyl)-2-propene (7.14 min); and 6, tetradecanoic acid.

35
 Journal of Chromatographic Science, Vol. 34, January 1996

MDA, respectively. Although less potent, MMDMA and MMDA are Experimental
reported to possess stimulant and hallucinogenic activity com­
parable with MDMA (7). Thus, myristicin is another example of GC—MS analysis
a readily available, naturally occurring precursor chemical that These analyses were performed using a Hewlett-Packard
may be used in the synthesis of potential drugs of abuse. Addi­ 5970B mass selective detector (Palo Alto, CA). The ionization
tionally, 3-methoxy-4,5-methylenedioxybenzaldehyde is com­ voltage was 70 eV, and the source temperature was 220°C. The
mercially available, and this uncontrolled aldehyde can also be samples were dissolved in methanol (1 mg/mL), and 0.5 μL of
used to prepare MMDA derivatives. We report the results of the each sample was introduced into the mass spectrometer via a
gas chromatographic-mass spectrometric (GC—MS) analysis of gas chromatograph equipped with an HP-1 fused-silica column
nutmeg oil and the reaction products obtained from the syn­ (12 m×0.20-mm i.d., 0.33-μm thickness of methylsilicone).
thesis of MMDMA from the oil and from the commercially avail­ The column temperature was programmed from 70°C to 150°C
able aldehyde precursor. at a rate of 15°C/min and from 150°C to 250°C at a rate of
25°C/min with a hold time of 6 min. The
split ratio for the GC was 10:1, and the sam­

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ples eluted in approximately 9 min.

Liquid c h r o m a t o g r a p h i c analysis
Liquid chromatographic analyses were
conducted using a Laboratory Data Control
Constametric 3000 pump (Riviera Beach,

Figure 3. Gas chromatographic-mass spectral analysis of the product obtained on treatment of nutmeg oil with HBr: A, chromatogram; B, mass spectrum of the
brominated myristicin product (2-bromo-1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propane).

36
Journal of Chromatographic Science, Vol. 34, January 1996

FL), a 3100 spectromonitor UV detector, a

CI 4100 integrator, and a Rheodyne 7125 in­
jector (Cotati, CA). The analytical column
(25 cm×3.9-mm i.d.) was packed with Bond-
clone C (Phenomenex; Torrance, CA). The
1 8

analytical column was preceded by a direct

connect (Alltech Associates; State College,
PA) guard column packed with CO:Pell ODS
(Whatman; Clifton, NJ). The mobile phase
consisted of p H 3.0 phosphate b u f f e r -
acetonitrile-triethylamine (600:100:1) at a
flow rate of 1.25 mL/min. The pH 3.0 phos­
phate buffer was prepared by mixing 9.2 g
monobasic sodium phosphate in 1 L of

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double-distilled water and adjusting the pH
to 3.0 with H P O . The UV absorbance de­
3 4

tector was operated at 254 nm and 0.2 AUFS.

Scheme 2. Mass spectral fragmentation for 2-bromo-1-(3-methoxy-4,5-methylenedioxyphenyl)-2-
A 15-μL aliquot of each c o m p o u n d i n
propane. methanol (1 mg/mL) was injected into the
liquid chromatograph.

Figure 4. Gas chromatographic-mass spectral analysis of the product obtained on treatment of the brominated nutmeg oil with methylamine: A , chromatogram;
B, mass spectrum of M M D M A (N-methyl-l-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanamine).

37
 Journal of Chromatographic Science, Vol. 34, January 1996

Bromination reactions aqueous acid solution was washed with ether and then made
A suspension of nutmeg oil in 48% HBr was stirred vigor­ basic (pH 12) by the addition of NaOH pellets. The aqueous
ously at room temperature for 7 days. The reaction was then base solution was extracted with ether, and the combined ether
quenched with the addition of crushed ice and extracted with extracts were evaporated to dryness under reduced pressure.
ether. The ether extracts were combined, washed with water, The resulting oil was analyzed directly.
and evaporated to dryness under reduced pressure, and the re­
sultant product oil was analyzed directly by GC—MS. Synthesis of 1-(3-methoxy-4,5-methylenedioxyphenyl)-
2-nitro-1-alkenes
Amination reactions A solution of 3-methoxy-4,5-methylenedioxybenzaldehyde
The crude bromination product was dissolved in methanol and n-butylamine in benzene was stirred at reflux for several
containing 40% aqueous methylamine and stirred at room tem­ hours. The water generated during imine formation was re­
perature for several days. The reaction mixture was evaporated moved with a Dean-Stark trap. The reaction mixture was cooled
to dryness, and the resultant oil was dissolved in 10% HC1. The to room temperature, and the solvent was evaporated under re­
duced pressure to yield the intermediate

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n-butylimine as a yellow oil. The imine was
dissolved in a solution of the appropriate ni-
troalkane and glacial acetic acid and stirred
at reflux for several hours. The reaction mix­
ture was cooled, poured over crushed ice,
and acidified with concentrated HCl to yield
the crude nitroalkenes as dark, highly col­
ored oils. The product oils were crystallized
and recrystallized from 2-propanol.

LAH reduction method for the synthesis

of the 1-(3-methoxy-4,5-methylene-
dioxyphenyl)-2-alkylamines
A solution of l-(3-methoxy-4,5-methyl-
enedioxyphenyl)-2-nitro-l-alkene in dry
tetrahydrofuran (THF) was added dropwise
over a period of several minutes to a cooled
(ice bath), stirred suspension of lithium alu­
minum hydride (LAH) in dry THF. After the
addition was complete, the reaction mixture
was stirred at room temperature for several
minutes, then at reflux for an hour. The re­
action mixture was cooled, and the excess
lithium aluminum hydride and salts were
Scheme 3. Mass spectral fragmentation for MMDMA.
decomposed by the successive addition of
water, 5N NaOH, and water. After stirring
an additional few minutes, the mixture was
filtered, the solids were washed with THF,
and the filtrate and washings were combined
and evaporated under reduced pressure to
yield a dark oil. The oil was suspended in
aqueous acid and washed with benzene. The
aqueous solution was made alkaline by the
addition of NaOH pellets, and the resulting
alkaline suspension was extracted w i t h
methylene chloride. The combined methyl­
ene chloride extracts were washed with
water and evaporated under reduced pres­
sure to yield a yellow oil that was dried
under high vacuum. The 1-(3-methoxy-4,5-
methylenedioxyphenyl)-2-alkylamine bases
were dissolved in anhydrous ether, and HCl
gas was added to yield the hydrochloride
Scheme 4. Synthesis of MMDMA and derivatives from 3-methoxy-4,5-methylenedioxybenzaldehyde.
salts.

38
Journal of Chromatographic Science, Vol. 34, January 1996

Synthesis of 1-(3-methoxy-4,5-methylenedioxyphenyl)- The reaction mixture was monitored periodically, and concen­
2-propanone trated HCl was added to maintain the pH at neutrality. The re­
A mixture of l-(3-methoxy-4,5-methylenedioxyphenyl)-2- action mixture was evaporated under reduced pressure to yield
nitro-l-propene, iron, ferric chloride in toluene, water, and a white solid. The solid was suspended in water, cooled in an ice
concentrated HCl was stirred vigorously and warmed overnight. bath, and slowly acidified by the addition of concentrated HCl.
The reaction mixture was cooled to room temperature and fil­ The aqueous acid was washed with methylene chloride, then
tered, and the solid mass was washed with water and toluene. made alkaline by the addition of NaOH pellets. The aqueous
These washings were combined with the original reaction sol­ basic suspension was extracted with methylene chloride, and
vents, and the toluene and water layers were allowed to sepa­ the extracts were combined and evaporated under reduced
rate. The toluene solution was washed successively with 3N pressure to yield a light yellow oil that was dried under high
HCl, water, saturated sodium bicarbonate, and water. The vacuum. The oil was dissolved in anhydrous ether, and HCl
toluene solution was filtered and dried over anhydrous potas­ gas was added to form the hydrochloride salt. Recrystallization
sium carbonate. Filtration followed by evaporation of the filtrate from mixtures of anhydrous ether and absolute ethanol yielded
solvent gave the crude ketone as a yellow oil. Distillation under the MMDMA HCl as yellow needles.

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reduced pressure yielded l-(3-methoxy-4,5-methylene-
dioxyphenyl)-2-propanone as a light yellow oil.
Results and Discussion
Reductive amination method for the synthesis of MMDMA
A solution of l-(3-methoxy-4,5-methylenedioxyphenyl)-2- The GC—MS analysis of commercially available nutmeg oil is
propanone, methylamine, and sodium cyanoborohydride in shown in Figure 1. The chromatogram in Figure 1A suggests at
methanol was stirred at room temperature for several days. least five components of relatively significant concentration,

Figure 5. Gas chromatographic—mass spectral analysis of the amine product obtained on reduction of 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-nitropropene
with lithium aluminum hydride: A, chromatogram; B, mass spectrum of MMDA (1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanamine).

39
 Journal of Chromatographic Science, Vol. 34, January 1996

and the first three peaks (peaks 1,2, and 3) are various terpene donating ring substituents, particularly alkoxy groups such as
analogues. The mass spectra obtained for these peaks show methoxy or methylenedioxy, make myristicin an obvious alter­
matches with a high degree of probability for the spectra of native or designer analogue of safrole (7). When myristicin is
γ-terpinene, α-terpinolene, and terpinen-4-ol. Terpinen-4-ol, substituted for safrole in the bromination—amination synthetic
which eluted at 4.87 min (peak 3), appears to be the terpene of method described previously, the product obtained is N-methyl-
highest concentration in the nutmeg oil. Peak 4, which eluted l-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanamine
at 5.60 min, was identified as safrole (l-(3,4-methylene- (MMDMA), a known hallucinogenic and stimulant drug (7).
dioxyphenyl)-2-propene), a common precursor substance The chromatogram in Figure 2 was obtained from the GC—MS
bearing the carbon skeleton for the 3,4-methylenedioxyam- analysis of a methanol extract of nutmeg spice (ground nutmeg).
phetamines. The major component in the nutmeg oil eluting at The large peak in the 5-min region (peak 1) is the terpinen-4-ol,
7.03 min (peak 5) is a trisubstituted arylpropene, l-(3-methoxy- and the small peak at 5.64 min (peak 2) is safrole. The larger
4,5-methylenedioxyphenyl)-2-propene (Figure 1B). T h e peak at 6.28 min (peak 3) matches the mass spectrum for l-(3,4-
common name for this arylpropene is myristicin, and it is dimethoxyphenyl)-2-propene, an arylpropene not observed as a
simply the m-methoxy derivative of safrole. In previous studies significant component in nutmeg oil. The major peak at 7.02

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(6) it was shown that the propene side chain of safrole can be min (peak 4) is myristicin, and the partially resolved secondary
functionalized at the 2-position by treatment with HBr, and the peak at 7.14 min (peak 5) yields a mass spectrum corresponding
resulting bromination product is treated with amines such as to l-(3,4,5-trimethoxyphenyl)-2-propene. The later eluting
m e t h y l a m i n e for the preparation of 3,4-methylene- major peak at 8.88 min (peak 6) matches the mass spectrum for
dioxymethamphetamine (MDMA, "Ecstasy"). The known central tetradecanoic acid. This acid would not be a major component
nervous system effects of phenethylamines with electron- in the nutmeg oil, which is isolated by distillation. Although the

Figure 6. Gas chromatographic—mass spectral analysis of the product obtained on reductive hydrolysis of 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-nitropropene:
A, chromatogram; B, mass spectrum of 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanone.

40
Journal of Chromatographic Science, Vol. 34, January 1996

extract from ground nutmeg shows some components not found methylamine produced a basic fraction (Figure 4) consisting
in nutmeg oil, both products are rich in the key precursor sub­ primarily of MMDMA (peak 2 at 8.49 min in Figure 4A) and a
stance, myristicin. detectable amount of MDMA (peak 1 at 7.11 min). These results
The chromatogram and mass spectra in Figure 3 show the demonstrate that MMDMA can be obtained from the natural
analysis of a sample of nutmeg oil treated with HBr. Although product myristicin in a synthetic procedure involving activation
the chromatogram in Figure 3A suggests a complex mixture in of the propene side chain with HBr, followed by bromine dis­
the crude reaction product, the large peak eluting at 8.97 min placement with methylamine. The mass spectrum for the major
yields a mass spectrum (Figure 3B) consistent with the addition amine, MMDMA (Figure 4B), shows a molecular ion of low
of HBr across the side chain double bond of myristicin to yield abundance and the expected base peak at m/z 58 from the loss
the 2-bromo derivative (Scheme 1). The major fragments in the of the substituted benzyl radical, which yields the N-methyl-
mass spectrum in Figure 3B correspond to the loss of bromine propylirnine cation (Scheme 3). The other high mass frag­
from the molecular ion to yield the peak at m/z 193 and the 3- ments at m/z 165 and 166 are the substituted benzyl carboca­
methoxy-4,5-methylenedioxybenzyl carbocation base peak at tion and radical carbocation, respectively. These latter
m/z 165 (Scheme 2). fragments are observed for aromatic compounds having an

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The complex series of peaks between 4 and 8 min in the alkyl side chain of propyl or larger (8) and are common frag­
chromatogram in Figure 3A shows quite similar mass spectra ments in phenethylamines, especially those with electron-
indicative of the isomeric products resulting from addition of donating aromatic substituents. Although the mass of these
HBr to the various terpene derivatives. A commercial sample of ions varies with the nature and extent of aromatic ring substi­
terpinen-4-ol, a major terpine component identified from tution, this fragmentation process is observed in 3,4-methylene-
nutmeg oil, was treated with HBr under identical reaction con­ dioxyamphetamines (9) and related compounds of forensic in­
ditions. GC—MS analysis of the resulting product showed a terest (10,11).
complex chromatogram in the 4- to 8-min range yielding sim­ Scheme 4 illustrates another common approach to the syn­
ilar mass spectra. These spectra are essentially identical to thesis of phenethylamines and related compounds applied to
those observed in the chromatogram in Figure 3A and confirm the preparation of MMDMA and derivatives. The requisite alde­
these components as various isomeric bromoterpenes. hyde, 3-methoxy-4,5-methylenedioxybenzaldehyde, is com­
Treatment of the brominated nutmeg oil product with mercially available and yields the corresponding nitroalkene
upon treatment with the appropriate nitroalkane. Reduction of
the intermediate nitroalkenes with lithium aluminum hydride
yields the corresponding primary amine products, l-(3-
methoxy-4,5-methylenedioxyphenyl)-2-ethanamine, -2-
propanamine (MMDA), and -2-butanamine. I n addition, the
nitropropene intermediate ( R = C H ) was subjected to reductive
3

hydrolysis to yield the l - ( 3 - m e t h o x y - 4 , 5 - m e t h y l e n e -

dioxyphenyl)-2-propanone. Reductive amination of this ketone
with methylamine provided MMDMA. The structures of all
products were confirmed by standard spectroscopic techniques
(i.e., infrared, nuclear magnetic resonance, and mass spectro-
metric techniques), and the purity of all products was estab­
lished by chromatography.
Figure 5 shows the analysis of the amine fraction obtained
following lithium aluminum hydride reduction of the nitro­
propene ( R = C H ) . The chromatogram in Figure 5A indicates
3

one major component whose mass spectrum (Figure 5B) is

consistent with MMDA. The base peak at m/z 44 is the primary
propylimine, and the peaks at m/z 165 and 166 are the substi­
tuted benzyl species previously described and illustrated in
Scheme 3. Lithium aluminum hydride reduction of the ni-
troethene ( R = H ) and nitrobutene ( R = C H C H ) intermediates
2 3

provided the corresponding l-(3-methoxy-4,5-methylene-

dioxyphenyl)-2-ethanamine and -2-butanamine products, re­
spectively, in good yield and high purity. These derivatives
yielded mass spectra comparable with that obtained for
Figure 7. Reversed-phase liquid chromatographic analysis of MMDA and
MMDMA with base peaks characteristic of amine-dominated
derivatives. Peaks: 1, 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-
fragmentation (m/z=30 and 58, respectively) and with peaks at
ethanamine (5.02 min); 2, 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-
m/z 165 and 166 representative of the substituted benzyl
propanamine ( M M D A , 7.80 min); 3, N-methyl-1-(3-methoxy-4,5-
methylenedioxyphenyl)-2-propanamine (MMDMA, 9.05 min); and 4,
species.
1-(3-methoxy-4,5-methylenedioxyphenyl)-2-butanamine (12.69 min). Figure 6 illustrates the results of analysis of the product
from reductive hydrolysis of the nitropropene shown in Scheme

41
 Journal of Chromatographic Science, Vol. 34, January 1996

4. The resulting product mixture is primarily the l-(3-methoxy- Conclusion

4,5-methylenedioxyphenyl)-2-propanone eluting at 8.12 min
(Figure 6A) and producing the mass spectrum in Figure 6B. GC—MS methods allowed for the specific identification of
The base peak in the spectrum is the substituted benzyl carbo­ the starting materials, intermediates, and products involved
cation at m/z 165. The remaining high mass fragment is the in the preparation of MMDMA and derivatives from nutmeg
molecular ion at m/z 208. The 2-propanone is a key precursor oil (myristicin) and commercially available 3-methoxy-4,5-
that can be reductively aminated with various amines to yield methylenedioxybenzaldehyde. Reversed-phase liquid chro­
a variety of N-substituted-1-(3-methoxy-4,5-methylene- matography separated all MMDMA derivatives, and resolution
dioxyphenyl)-2-propanamine derivatives, including the resulted from relative differences in hydrophobic surface area
N-methyl derivative MMDMA. of the derivatives.
The four amines of this study display similar gas chromato­
graphic retention, and complete resolution was not obtained
under the conditions investigated. Thus, reversed-phase liquid References
chromatographic separation was investigated, resulting in the

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chromatogram shown in Figure 7. In the acidic mobile system 1. R.S. Frank. T h e clandestine drug laboratory situation in the United
States. J. Forensic Sci. 28: 18 (1983).
used for this separation, the amines are in the protonated form,
2. F.T. Noggle, J. DeRuiter, and C.R. Clark. Liquid chromatographic
and the protonated triethylamine in the mobile phase serves as determination of the e n a n t i o m e r i c c o m p o s i t i o n of m e t h a m -
a competitor for silanol sites on the stationary phase. This dy­ phetamines prepared from ephedrine and pseudoephedrine. Anal.
namic saturation of silanol sites prevents the peak tailing com­ Chem. 58: 1643–48 (1986).
monly observed for amines in reversed-phase liquid chro­ 3. F.T. Noggle, J. DeRuiter, and C . R . Clark. Methods for the analysis
and characterization of forensic samples containing amphetamines
matography. The four amines are well-resolved in this system,
and related amines. J. Chromatogr. Sci. 28: 529–36 (1990).
and the unbranched primary amine, the 2-ethanamine, has 4. F.T. Noggle, C . R . Clark, A . K . Valaer, and J. DeRuiter. Liquid chro­
the lowest capacity factor. The α-methyl-branched primary matographic and mass spectral analysis of N-alkyl analogues of
amine, the 2-propanamine (MMDA), elutes second, and this 3,4-methylenedioxyamphetamine. J. Chromatogr. Sci. 26: 410–15
amphetamine derivative is well-resolved from its N-methyl (1988).
5. Chemical Diversion and Trafficking Act, March, 1989.
derivative MMDMA, which is the third component to elute in
6. F.T. Noggle, C.R. Clark, and J. DeRuiter. Gas chromatographic and
this chromatogram. Peaks 2 and 3 in the chromatogram each mass spectral analysis of samples from a clandestine laboratory in­
represent the addition of a single methyl group to the previ­ v o l v e d in the synthesis of "Ecstasy" from sassafras oil. J. Chro­
ously eluting component (peaks 1 and 2, respectively). The en­ matogr. Sci. 29: 168–73 (1991).
hanced retention observed upon the addition of one methyl 7. A . T . Shulgin, T. Sargent, and C . Naranjo. Animal pharmacology
and human psychopharmacology of 3-methoxy-4,5-methylene-
group is caused by the increase in solute hydrophobic surface
dioxyphenylisopropylamine ( M M D A ) . Pharmacology 10: 12-18
area. The significant resolution of these compounds indicates (1973).
the sensitivity of hydrocarbon stationary phases to small 8. F.W. McLafferty. Interpretation of Mass Spectra, 3rd ed. University
changes in solute hydrophobicity. Peaks 2 and 3 are baseline- Science Books, Mill Valley, C A , 1980, pp 186–88.
resolved in this system, which has retention differences of more 9. C . R . Clark, F.T. Noggle, J. DeRuiter, and S. Andurkar. Analysis of
than 1 min. The retention difference for these two compounds 3,4-methylenedioxyphenyl-2-propanamine and 3,4-methylene-
dioxyamphetamines prepared from isosafrole. J. Chromatogr. Sci.
was approximately 0.1 min under the gas chromatographic 32: 393–402 (1994).
conditions used in this study. Peaks 3 and 4 in Figure 7 further 10. F.T. Noggle, C . R . Clark, P. Pitts-Monk, and J . DeRuiter. Liquid
illustrate this point as these two amines differ only in the po­ c h r o m a t o g r a p h i c a n d mass s p e c t r a l a n a l y s i s of 1-(3,4-
sition of one methyl group. The N-methyl-2-propanamine dimethoxyphenyl)-2-propanamines: analogues of M D M A . J. Chro­
MMDMA and the primary amine 2-butanamine have the same matogr. Sci. 29: 253–57 (1991).
11. C . R . Clark, J . DeRuiter, A . Valaer, and F.T. Noggle. Gas chro­
molecular weight and differ only in N-methyl versus C-methyl matographic-mass spectrometric analysis of designer butanamines
substitution. This small difference, however, allows for baseline related to M D M A . J. Chromatogr. Sci. 33: 328-37 (1995).
resolution in this liquid chromatographic system. Manuscript accepted July 10, 1995.

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