The NBOMe series of designer drugs:

preliminar GC-EI/MS findings concerning

NBOMe-2C-B and NBOMe-2C-C
Dieter Waumans, Ana Paula Poles, Tomas Somers and Jan Tytgat
Laboratory of Toxicology (KU Leuven), Campus Gasthuisberg O&N2, Herestraat 49 PO Box 922, B-3000 Leuven, Belgium

Introduction. The NBOMe-series of designer drugs are the N-ortho-anisyl analogues of the "classic phenethylamines", especially of the
2C-X class (i.e. 2C-B, 2C-C and 2C-I). The NBOMe-2C-X analogues can easily be purchased via the internet. Reported dosages vary
within the 0.1-1mg range. Due to the free availability of these compounds and the relatively low user dosage, we were prompted to investigate
their analytical behaviour within the standard operating procedures of the laboratory. We chose NBOMe-2C-B and its chlorine-analogue
NBOMe-2C-C as model compounds.
Methods. NBOMe-2C-B (1) and NBOMe-2C-C (2) were synthesized from the corresponding phenethylamines by NaBH4-reduction of their
condensation product with o-methoxybenzaldehyde. Analytical samples were prepared following a standard SPE protocol. Samples were
analysed either underivatized (MeOH) or after derivatization (TMS (BSTFA) and HFBA) via GC-EI/MS (Agilent 6890N GC + 5975B MS).
Underivatized + TMS-derivatization: GC-method: 65ºC (2min) -> 100ºC (0min, 35ºC/min) -> 325ºC (7min, 4.5ºC/min); MS-method: synchronous
SIM/Scan (96 SIM-compounds), TIC scan range: 36-500amu, EI-MS (70eV) / HFBA-derivatization: GC-method: 100°C (2min) -> 250°C (0min,
10°C/min -> 310°C (6min, 30°C/min); MS-method: TIC scan range 36-700amu, EI-MS (70eV)
Results. GC-analysis of 1 and 2 resulted in artifact formation. As shown in Fig. 1 and 2, the target peak for both compounds was an overlap
of coeluting substances. Based on the deconvoluted mass spectra, we postulated the presence of 1 and 2 in combination with either an
O
H O
artifact or a synthesis impurity. Two structures
H
N N were proposed, namely a tetrahydroisoquinoline
O
Br Cl
O
(THIQ) and an imine (Fig. 3). The THIQ should -
O NBOMe-2C-B, (1) O NBOMe-2C-C, (2)
in theory - give fragments corresponding to a
FIG. 1 FIG. 2 retro-Diels Alder (rDA), but those were not 121
121

observed. The imine is a synthesis intermediary

Ion 121.00 (120.70 to 121.30)
Ion 148.00 (147.70 to 148.30)
Ion 150.00 (149.70 to 150.30)
Ion 121.00 (120.70 to 121.30)
Ion 150.00 (149.70 to 150.30)
Ion 185.00 (184.70 to 185.30)

formed by condensation of 2C-X with o-

Ion 346.00 (345.70 to 346.30)
Ion 348.00 (347.70 to 348.30)
Ion 302.00 (301.70 to 302.30)
150
148

anisylaldehyde. The detected fragments could be 91

150
91

theoretically identified (Fig. 3 and 4). The identity

77 185,186
346,348 187,188
65 105
65 77

38.00 38.40 38.80 39.20

39.50 40.00 40.50 41.00 41.50 42.00 40 80 120 160 200 240 280 320

of the the imine was unequivocally proven by

40 80 120 160 200 240 280 320

synthesis of the imine and GC-MS analysis. O

H
N
148 148
O
Br
121 121
121
O

NBOMe-2C-B, (1)
O
The question arose whether this imine was
H
N

Cl
O
formed as a thermal dehydrogenation artefact or
O

was present as an impurity from the synthesis.

150
302
346
348
91
91
NBOMe-2C-C, (2)
91

65
77
105
133
199 201
377 379
65 77 199,201
229,231
230,232
65
77

105 133
304

333
Since the imine could not be detected by LC-
MS/MS (AB SCIEX 3200 QTRAP, Shimadzu
185

40 80 120 160 200 240 280 320 360 40 80 120 160 200 240 280 320 360
40 80 120 160 200 240 280 320

Prominence UFLCXR), we are inclined to believe

FIG. 3 121
148
FIG. 4 that it is formed as a thermal dehydrogenation
O
artefact.
NBOMe-2CB
N

148 O
Cl
O

121
artefact/impurity?

The 1-H2 and 2-H2 artifacts show a [M-MeO]+-

O
302
N
91 X O
O

346
O

N m/z 377-379 65
77

105 133
185
304

333
fragment that in the case of 1 and 2 is easily
identifiable because of their halogen isotopic
348 Br O
91
77
O 40 80 120 160 200 240 280 320

105
O
133

40
65

80 120 160
199

200
201

240 280 320 360

377 379
X
O
N
distribution patterns (Fig. 4). Since the most
Br
O

N
148 O
abundant EI-MS fragments of 1 and 2 are of low
O

O
121 O
N

O
O
-MeO
specificity (Fig. 5), the presence of the
O N
-MeO
Br
O
X N dehydrogenated artefacts allows a better
Br
N

O
a O rH + i

-HCN
O
Br
O

N
346
348
O identification because of the presence of the [M-
m/z 346-348
MeO]+-fragment.
91

O 77

m/z 148 m/z 121 105

133
O 65 199 201
377 379

40 80 120 160 200 240 280 320 360

Trimethylsilylation was not a viable solution (Fig.

121
FIG. 5 NBOMe-2CB.TMS FIG. 6 6). The derivatization was not complete
NBOMe-2CB NBOMe-2CB.TMS

(secondary nitrogen), the EI-MS fragments

O

91
150 H
N

O
a O
HN
-NHCH2 O O Si
remained of low specificity and there seemed to
199,201
229,231
230,232
X
O
m/z 150 m/z 121 Br
N

O
O Si
N be a certain degree of on-column degradation of
65 77

40 80 120 160 200 240 280 320 360

NBOMe-2CB-H2
O
Br
O
O

m/z 451-453
the TMS derivative.
a

Derivatization with HFBA gave specific mass

39.00 40.00 41.00 42.00 43.00 44.00 45.00

121 O O

X
HN
X
H
HN
121 Si
N
m/z 222 spectra (1.HFBA, Fig. 7) but also pronounced
O

a
O O

rH + a
O 222
O
degradation of the compound. In the case of 1,
91
150
O O -CH2N.TMS
we observed the formation of e.g. 2C-B and 4-
bromo-2,5-dimethoxybenzyl alcohol.HFBA.
91
185,186
187,188
X X
H
H m/z 121
65 77 O O
77
[M-Me]+ O
40 80 120 160 200 240 280 320

40 80 120 160
199,201

200
229,231

240 280 320 360 400

436,438

440
FIG. 7 121

F F
F
F
F
F
O
O F
N

Conclusions. It appears that the analysis of 1 and 2 with GC-EI/MS faces several limitations: 91 Br
O
O

thermal artifact formation, EI-MS spectra of low specificity and standard derivatization methods 242,244

are inefficient. Additionally, it is worth mentioning that EI-MS-based identification of 1 and 2 is

only possible based on the mass spectra of their corresponding dehydrogenated artifacts.
Further study is necessary, but we suggest that LC-based methods may be better suited for 575, 577

this compound series. .

50 150 250 350 450 550