Synthesis of 2C-B From Anise Oil
Synthesis of 2C-B From Anise Oil
Synthesis of 2C-B From Anise Oil
O
up the residue in 100 mL aqueous NaOH (20%) (25 mL MeOH as co-solvent)
yielded 4.1 g 4-methoxyphenol as a white crystalline product after the usual
O 137 work-up and purification steps.
O O D : Reimer-Tiemann formylation of 4-methoxyphenol: 124.1 g 4-methoxyphenol
H was dissolved in NaOH solution (320 g NaOH in 400 mL water). In total, 161 mL
O
53
chloroform was added. The usual work-up and steam distillation yielded 109.8 g
109
81
of a clear yellow oil that did not solidify upon standing at room temperature
39
63 (GC/MS: 94% 2-hydroxy-5-methoxybenzaldehyde).
C E : Methylation of 2-hydroxy-5-methoxybenzaldehyde: The yellow oil from D was
40 60 80 100 120 140 160
166
used without further purification. A 250 mL RB flask was charged with 100 mL
acetone, 14 g anhydrous potassium carbonate and 10 g 2-hydroxy-5-methoxy-
O OH benzaldehyde; the mixture was brought at reflux temperature and 11 g dimethyl
O sulfate was added. The reaction was continued for 4 hours. The solvent is
O
evaporated and the crude end product crystallized in cold water. Recrystallization
O
from EtOH/water yielded 8.3 g 2,5-dimethoxybenzaldehyde (GC/MS: 98%+
63 95
2,5-dimethoxybenzaldehyde)
151
53
106 120 SYNTHESIS OF 4-BROMO-2,5-DIMETHOXYPHENYLETHYLAMINE (FIG. 2)
79
41
137
D A 250 mL RB flask was charged with 16.6 g 2,5-dimethoxybenzaldehyde,
40 60 80 100 120
1.6 g NaOAc and 50 mL nitromethane. Refluxing for 4h yielded 14.4 g of the
140 160
corresponding nitrostyrene [1] after recrystallization.
5.0 g of 2,5-dimethoxylphenyl-2-nitroethene was added to a solution of 4.0 g
OH
sodium borohydride in 100 mL isopropanol. This yielded 4.2 g of a yellow oil
O
after decomposition of the excess borohydride followed by the usual work-up (B).
O The 2,5-dimethoxyphenyl-2-nitroethane was dissolved in 100 mL isopropanol with
E O
8 molar equivalents Zn and 3.5 molar equivalents HOAc (relative to amount of Zn).
O This yielded 2.0 g of 2,5-dimethoxyphenylethylamine as a faintly yellow oil (C).
O
The obtained amine was brominated following Shulgin’s method to yield 2.1 g
2C-B as the hydrochloride salt (D).
FIGURE 1 : Anethole is oxidized to anisaldehyde (A), which after isolation is subjected to a Baeyer-
Villiger oxidation reaction with performic or peracetic acid (B). The O-formyl-4-methoxyphenol
obtained this way is hydrolyzed (C). 4-Methoxyphenol is subsequently formylated using CONCLUSION:
the Reimer-Tiemann method (D) and the obtained 2-hydroxy-5-methoxybenzaldehyde is It is possible to synthesize phenylethylamine derivatives different from PMA and
methylated with dimethylsulfate to 2,5-dimethoxybenzaldehyde (E). PMMA using anethole as precursor. The total yield of 2,5-dimethoxybenzaldehyde
The mass spectra of 2-hydroxy-5-methoxybenzaldehyde and 2,5-dimethoxybenzaldehyde
are shown.
from anethole varies between 15-25%. The total yield of 2C-B from 2,5-dimethoxy-
benzaldehyde amounts ca. 20% (using easily procurable compounds).
O O
FIGURE 2a : The mass spectra of the intermediary products are shown: 2,5-dimethoxyphenyl-2-nitroethene [1], NO2
2,5-dimethoxyphenyl-2-nitroethane [2], 2,5-dimethoxyphenylethylamine [3], 4-bromo-2,5-dimethoxy- O
phenylethylamine (2C-B) [4] A
B O O
209
152
[1] O [3] O O
NO2
NH2
NO2
O 133 O
77
162 137 O
147
51
91 105
63
119 121
77 91 181
65
39
178 39 51
108
C O O
40 60 80 100 120 140 160 180 200 40 60 80 100 120 140 160 180 NH2 NH2
164
D
230 Br
[2] O [4] O O O
NO2
NH2
150
211 Br
O
O
135
77 77
91
121 215
FIGURE 2b : 2,5-dimethoxybenzaldehyde is reacted with
105 91 105 nitromethane to yield the corresponding nitrostyrene (A).
65 53 201 259
39 51 39 121 The latter is reduced with sodium borohydride to
the nitroethane (B). The nitro functional group is
40 60 80 100 120 140 160 180 200 40 60 80 100 120 140 160 180 200 220 240 260 reduced by Zn/HOAc (C) and the obtained
phenylethylamine is brominated to yield 2C-B (D).