iv
S. Hosztafi, J. Marton/Chemical Papers
6-O-acetyldihydrocodeine) was prepared analogously
to IIIa starting from 6-O-acetyldihydrocodeine (IIb,
10.06 g, 29.3 mmol). Yield: 8.08 g (71 %). M.p.: 190–
(30 mL) were added to the solution. The reaction mix-
ture was heated at 100◦C for 2 h, and then it was
allowed to stand at room temperature overnight (ca.
16 h). The double salt of the aminocodeine – SnCl2
was precipitated from the acidic solution and the salt
was filtered and dissolved in water (120 mL); the solu-
tion was then saturated with hydrogen sulfide (Warn-
ing: use fume cupboard!) in order to precipitate SnS.
The latter was filtered and the filtrate was saturated
with potassium carbonate (pH ≈ 9.5). The filtrate was
extracted with chloroform and the combined extract
was dried (Na2SO4). The solution was concentrated
under reduced pressure and the residue was recrystal-
lized from ethanol.
1
191◦C. H NMR (CDCl3), δ: 7.72 (s, 1H, H-2), 5.40
(m, 1H, H-6), 4.75 (d, 1H, H-5), 3.90 (s, 3H, 3-OCH3),
3.51 (d, 2J10β,10α = 20.0 Hz, 1H, H-10β), 3.40 (m, 1H,
H-9), 2.75 (m, 1H, H-10α), 2.70–2.60 (m, 2H, H-14,
H-16), 2.40 (s, 3H, NCH3), 2.25 (m, 1H, H-16), 2.20
(s, 3H, 6α-OCOCH3), 2.10 and 1.80 (m, 2H, H-15ax
and H-15eq). ESI-MS, m/z (Ir/%): 389 (67) [M + 1]+,
329 (44), 290 (75), 272 (100), 255 (35). C20H24N2O6
(388.41).
Hydrolysis of esters IIIa–IIIb
(5R,6S,9R,13S,14R)-1-Amino-7,8-didehydro-4,5
α-epoxy-6-α-hydroxy-3-methoxy-17-methyl-morphin-
an (Va, 1-aminocodeine, CAS RN: 49751-23-7) (Bog-
nár & Gaál, 1963; Cankař et al., 2013). Yield: 3.2 g
(65 %). M.p.: 228–230◦C; 228◦C (Ochiai & Nakamura,
6-α-O-Acetyl-1-nitro compound (IIIa, IIIb, 5.1
mmol) was dissolved in ethanol (50 mL), and 10
mass % NaOH (10 mL) was added to the solution.
The reaction mixture was stirred at 100◦C for 1 h.
Ethanol was evaporated in vacuum; then, water was
added to the residue and the mixture was extracted
with chloroform. The combined extracts were dried
(Na2SO4) and concentrated under reduced pressure to
yield a crystalline substance which was recrystallized
from ethanol.
1
1939). H NMR (CDCl3), δ: 6.15 (s, 1H, H-2), 5.70
(m, 1H, H-7), 5.25 (m, 1H, H-8), 4.80 (m, 1H, H-
5β), 4.1 (m, 1H, H-6), 3.80 (s, 3H, 3-OCH3), 3.45 (dd,
3
3J9α,10α = 6.0 Hz, J9α,14 = 3.5 Hz, 1H, H-9α), 2.70
2
(d, J10β,10α = 18.2 Hz, 1H, H-10β), 2.65–2.50 (m,
2H, H-14, H-16), 2.45 (s, 3H, NCH3), 2.37 (t, 1H, H-
2
3
(5R,6S,9R,13S,14R)-7,8-Didehydro-4,5-α-epoxy-
6-α-hydroxy-3-methoxy-17-methyl-1-nitro-morphinan
(IVa, 1-nitrocodeine, CAS RN: 19895-19-3) (Bognár
& Gaál, 1963). M.p.: 221–222◦C; 220–221◦C (Ochiai
& Nakamura, 1939). 1H NMR (CDCl3), δ: 7.70 (s, 1H,
H-2), 5.35 (m, 1H, H-7), 5.50 (m, 1H, H-8), 5.00 (d,
1H, H-5β), 4.50 (d, 1H, H-6), 3.85 (s, 3H, 3-OCH3),
3.55 (d, 2J10β,10α = 20.0 Hz, 1H, H-10β), 3.35 (m, 1H,
16), 2.10 (dd, J10α,10β = 18.2 Hz, J10α,9α = 6.1 Hz,
H-10α), 2.03 and 1.83 (m, 2H, H-15ax and H-15eq).
ESI-MS, m/z (Ir/%): 315 (100) [M + 1]+, 258 (35),
240 (24), 230 (46), 226 (41), 198 (56). C18H22N2O3
(314.38).
(5R,6S,9R,13S,14R)-1-Amino-4,5-α-epoxy-6-α-
hydroxy-3-methoxy-17-methyl-morphinan (Vb, 1-ami-
nodihydrocodeine). Yield: 2.2 g (48 %). M.p.: 209–
210◦C. 1H NMR (CDCl3), δ: 6.15 (s, 1H, H-2), 4.50 (d,
1H, H-5β), 4.00 (m, 1H, H-6), 3.80 (s, 3H, 3-OCH3),
3.10 (dd, 1H, H-9), 2.70 (d, 2J10β,10α = 17.7 Hz, 1H, H-
10β), 2.50 (m, 1H, H-14), 2.42 (s, 3H, NCH3), 2.10 (dd,
2
H-9), 2.72 (d, J10α,10β = 20.0 Hz, 1H, H-10α), 2.70–
2.60 (m, 2H, H-14 and H-16), 2.40 (s, 3H, NCH3), 2.30
(m, 1H, H-16), 2.15 and 1.80 (m, 2H, H-15ax and H-
15eq). ESI-MS, m/z (Ir/%): 345 (80) [M + 1]+, 327
(11), 287 (54), 271 (100), 253 (51), 242 (75), 226 (41).
C18H20N2O5 (344.36).
3
2J10α,10β = 17.7 Hz, J10β,9α = 5.8 Hz, 1H, H-10α),
2.25–1.75 (m, 4H, H-16ax, H-16eq, H-15ax, H-15eq).
ESI-MS, m/z (Ir/%): 317 (100) [M + 1]+, 260 (83),
242 (18), 232 (16), 214 (45). C18H24N2O3 (316.39).
(5R,6S,9R,13S,14R)-4,5-α-Epoxy-6-α-hydroxy-3-
methoxy-17-methyl-1-nitro-morphinan (IVb, 1-nitro-
dihydrocodeine). M.p.: 222–223◦C; 221◦C (Speyer &
1
Wieters, 1921). H NMR (CDCl3), δ: 7.75 (s, 1H, H-
Preparation of codeine-1-diazonium tetrafluoroborate,
VIa
2), 4.75 (d, 1H, H-5β), 4.10 (m, 1H, H-6), 3.93 (s, 3H,
2
3-OCH3), 3.50 (d, J10β,10α = 20.0 Hz, 1H, H-10β),
2
3.15 (m, 1H, H-9), 2.75 (d, J10α,10β = 20.0 Hz, 1H,
(5R,6S,9R,13S,14R)-7,8-Didehydro-4,5-α-epoxy-
6-α-hydroxy-3-methoxy-17-methyl-morphinan-1-dia-
zonium tetrafluoroborate (VIa, CAS RN: [330477-54-
8]) was prepared as following. 1-Aminocodeine (Va,
3.14 g, 10 mmol) was dissolved in a mixture of anhy-
drous ethanol (20 mL) and a 48 % aqueous tetraflu-
oroboric acid. Thereafter, the solution was cooled to
–10◦C and a 2 M sodium nitrite (5 mL) solution was
added dropwise under vigorous stirring. After the ad-
dition was complete, the stirring was continued at –
15◦C for 15 min. The reaction mixture was allowed to
warm up to room temperature and the precipitate was
filtered off and washed with anhydrous ethanol (2 ×
H-10α), 2.50 (m, 1H, H-14), 2.40 (s, 3H, NCH3), 2.25–
1.70 (m, 4H, H-16ax, H-16eq, H-15ax, H-15eq). ESI-MS,
m/z (Ir/%): 347 (100) [M + 1]+, 329 (13), 290 (91),
288 (39), 273 (59), 271 (51), 244 (44). C18H22N2O5
(346.38).
Synthesis of Va–Vb by 1-nitro derivatives reduction
The corresponding 1-nitro-derivative (14.5 mmol,
IVa, 1-nitrocodeine, 5.0 g; IVb, 1-nitrodihydrocodeine,
5.03 g) was dissolved in 2 M HCl (20 mL); then,
tin shavings (6.0 g, 50.5 mmol) and 37 mass % HCl
Unauthenticated
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