Journal of Chemistry
3
5-(1-(Bromomethyl)-1-hydroxyethyl)-2-methylcyclohex-2-
en-1-one 2d (mixture of diastereomers). 1H NMR (300 MHz,
CDCl3, δ):1.15 (3H, s, CH3), 1.59 (3H, s, CH3), 2.03–2.51 (5H,
m, 2 × CH2, CH), 3.22–3.39 (3H, m, OH and CH2Br),
6.59–6.70 (1H, m, �CH); 13C NMR (75 MHz, CDCl3, δ): 15.17
(C2-CH3), 22.12, 22.45 (C7-CH3), 25.81, 26.72 (C4), 37.92,
38.70 (C6), 41.36, 41.50 (C5), 41.86, 42.14 (C8), 71.51, 71.60
(C7), 134.44, 134.61 (C2), 144.86, 145.48 (C3), 199.69, 199.94
CH3), 1.66–1.84 (1H, m, 1H of CH2), 1.84–2.24 (1H, m, 1H of
CH2), 1.99, 2.196 (3H, 2d, J � 1.3 and 1.2 Hz, CH3C � ),
2.24–2.45 (1H, m, 1H of CH2) 2.56–3.03 (1H, m, 1H of CH2)
3.89–4.07 (2H, m, OH and Br-CH), 5.90–5.97 (1H, m, �CH),
10.00, 10.02 (1H, 2d, J � 7.8 and 7.6 Hz, CHO); 13C NMR
(75 MHz, CDCl3, δ): 17.70 (C3-CH3), 24.73, 26.26 and 26.38,
26.61 (gem-dimethyl), 31.42, 32.48 (C5), 39.17 (C4), 68.76,
69.02 (C6), 72.48, 72.51 (C7), 127.71, 129.45 (C2), 162.92,
162.02 (C3), 190.76, 191.13 (CHO); MS (EI, m/z (%)): 151
(12), 133 (6), 123 (7), 109 (7), 84 (86), 59 (100), 43 (46), 41
(28); C10H17BrO2 (249.15); MS (ESI, 180 eV): [M + H]+
249.04866, calc. 249.04802; C10H15BrO2 (248.15).
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(C1�O); ATR-IR: v � 3428, 2975; 1655; 1369; 1105; 960;
−1
655 cm ; MS (EI, m/z (%)): 230 (6), 228 (6), 153 (12), 137
(29), 121 (8), 110 (100), 95 (71), 81 (30), 57 (29), 41 (21); MS
(ESI, 180 eV): [M + H]+ 247.03314, calc. 247.03345;
C10H15BrO2 (246.13).
2-Methyl-5-(2-methyloxiranyl)-cyclohex-2-enone 3d (mix-
ture of diastereomers). 1H NMR (300 MHz, CDCl3, δ):
1.21–1.26 (3H, m, CH3-C-O), 1.66–1.71 (3H, m, CH3-C�C),
1.94–2.23 (3H, m, CH2 + CH), 2.27–2.39 (1H, m, 1H of
CH2), 2.42–2.54 (2H, m, CH2), 2.57–2.64 (1H, m, 1H of
CH2), 6.63–6.70 (1H, m, �CH); 13C NMR (75 MHz, CDCl3,
δ):15.44 (C2-CH3), 18.20, 18.71 (C7-CH3), 27.51, 27.70 (C4),
39.70, 40.08 (C6), 40.56, 41.08 (C5), 52.22, 52.62 (C8), 57.63,
57.73 (C7), 135.27, 135.32 (C2), 143.73, 143.96 (C3), 198.51,
198.56 (C1�O); MS (EI, m/z (%)): 151 (4), 148 (8), 133 (19),
123 (19), 109 (100), 108 (90), 91 (40), 82 (57), 67 (19), 54 (47),
39 (40); MS (ESI, 180 eV): [M + H]+ 167.10734, calc.
167.10725; C10H15BrO2 (166.21).
3. Results and Discussion
3.1. Synthesis of Bromoalcohol 2a. In connection with our
ongoing effort to prepare aminoalcohols from terpenes, we
first focused on the optimization of bromohydrin synthesis
to improve published results regarding limonene substrates.
In general, it is a reaction that proceeds at a yield of 70–87%
[29, 30]. Hence, we studied bromohydroxylation of limo-
nene 1a under various reaction conditions (Scheme 1).
Limonene 1a, which contains two different double bonds,
was mainly bromohydroxylated to 2a at the internal double
bond, while the external double bond remained unchanged
(Table 1). (e reaction proceeded smoothly at room tem-
perature under extremely mild conditions. Systematic in-
vestigation in the presence of various catalytic systems was
undertaken to define the best reaction conditions.
6-Bromo-7-hydroxy-3,7-dimethyl-octan-1-al 2e. 1H NMR
(400 MHz, CDCl3, δ): 0.90–0.96 (3H, m, CH3), 1.29 (3H, s,
CH3), 1.30 (3H, s, CH3), 1.23–1.47 (1H, m, 1H of CH2),
1.50–1.76 (2H, m, CH + 1H of CH2), 1.82–1.98 (1H, m, 1H of
CH2), 1.99–2.12 (1H, m, 1H of CH2), 2.15–2.43 (2H, m,
CH2), 3.87–3.92 (2H, m, OH and Br-CH), 9.70 (1H, s, CHO);
13C NMR (100 MHz, CDCl3, δ): 19.29, 19.99 (C3-CH3),
26.06, 26.15 and 26.25, 26.36 (gem-dimethyl), 27.19, 27.60
(C3), 31.00, 31.18 (C5), 35.56, 35.84 (C4), 50.34, 51.05 (C2),
70.45, 70.54 (C6), 72.49, 72.52 (C7), 202.57, 202.64 (CHO);
As depicted in Table 1, among the catalysts studied, CeO2
nanopowder and Dowex Marathon A, Cl form, appeared to
−
be the most suitable (entries 11, 12). (ey produced 2a in
70% yield within 15 min. But the differences in conversion
and yield were not so significant whether acidic or basic
catalysts were used. Probably, the generation of electrophilic
bromine species forming halonium ion intermediates with
the terpene followed by the nucleophilic attack of H2O was
possible at all polar catalyst surfaces. (e most efficient
catalyst (Dowex Marathon A) was subsequently used for the
next steps of the optimization.
−1
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ATR-IR: v � 3412, 2959, 2931, 2725, 1715, 1460, 1380 cm ;
MS (EI, m/z (%)):192 (4), 153 (4), 109 (8), 95 (10), 71 (42), 59
(100), 43 (33), 41 (17); MS (ESI, 180 eV): [M + H]+ 251.06462,
253.06248, calc. 251.06412, 253.06215; C10H19BrO2 (251.16).
6,10-Dimethyl-9,10-epoxy-undec-3-en-2-one 3e (mixture
of diastereomers). 1H NMR (300 MHz, CDCl3, δ): 0.87, 0.92
(3H, 2d, J � 6.7 Hz, CH3), 1.20 (3H, s, CH3), 1.24 (3H, s,
CH3), 1.27–1.70 (5H, m, CH, 2 × CH2), 1.96–2.27 (2H, m,
CH2), 2.18 (3H, s, CH3), 2.62 (1H, t, J � 5.9 Hz, CH-O), 6.01
(trans), 6.26 (cis) (1H, 2 d, J � 15.8 and 15.3 Hz, �CH-C�O),
6.64–6.88 (1H, m, -CH � ); 13C NMR (75 MHz, CDCl3, δ):
18.48, 18.53 and 19.36, 19.40 (gem-dimethyl), 24.70 (C6-
CH3), 26.19, 26.22 (C8), 26.27, 26.74 (C6), 32.28, 32.37 (C1),
33.17, 33.33 (C7), 39.78, 39.94 (C5), 58.00, 58.10 (C10),
64.15, 64.20 (C9), 129.87, 132.42 (C3), 146.14, 146.63 (C4),
(e effect of NBS was also evaluated (Table 2). Hence, the
increase of NBS amount had a boosting effect on the con-
version of 1a. When it was treated with at least 1.7 equiv-
alents of NBS in an aqueous solution of acetone, 1a was
totally converted (entries 7, 8). However, the maximum yield
of the corresponding bromoalcohol 2a (70%) was obtained
with only a slight surplus of NBS (1.3 equiv.) (entry 3). Using
a larger excess, various by-products coming probably from
side reactions (bromohydroxylation of exo-double bond)
during the formation of bromohydrin were detected by gas
chromatography.
(e yield of bromoalcohol 2a could be also influenced by
the nature of the solvent (Table 3). As can be seen in Table 3,
the highest efficient protocol was achieved in acetone,
methanol DMSO and THF (entries 1–5). In nitromethane,
acetonitrile, and dichloroethane less than 50% yield was
obtained (entries 6–8). An improvement of conversion and
yield was achieved in acetone by lowering the reaction
temperature to 0°C (entry 2). (e reaction of 1a with NBS in
ꢀ
198.26 (CHO); ATR-IR: v � 2959, 2925, 2873, 1672, 1626,
−1
1459, 1378, 1252,980 cm ; MS (EI, m/z (%)): 152 (2), 137
(12), 124 (6), 109 (29), 95 (49), 81 (40), 67 (24), 43 (100), 41
(39); MS (ESI, 180 eV): (M + H)+ 211.16921, calc. 211.16926;
C13H22O2 (210.31).
6-Bromo-7-hydroxy-3,7-dimethyl-oct-2-en-1-al 2f (mix-
ture of diastereomers). 1H NMR (300 MHz, CDCl3, δ):
1.20–1.59 (1H, m, 1H of CH2), 1.36 (3H, s, CH3), 1.37 (3H, s,