The Journal of Organic Chemistry
Article
147.2, 113.1, 44.3, 26.8, 22.7. MS (EI) m/z (%): 166.1 (33) [M]+•,
4.5.2. 2,3-Di-iso-butyl-1,4,4a,9a-tetrahydro-9,10-anthraquinone
(30b). 2,3-Diisobutyl-buta-1,3-diene (28b) (1.55 g, 9.35 mmol) was
used for the synthesis. Colorless solid; yield: 1.69 g (5 mmol, 54%). Rf
(silica gel, n-hexane/CH2Cl2 2:1): 0.35. mp 105−106 °C. H NMR
151.0 (10), 123.0 (100), 109.0 (43), 95.0 (76), 81.0 (33), 68.0 (28),
1
55.0 (15), 43.0 (29). The H data are in agreement with published
1
data.56
(CDCl3, 400 MHz): δ 8.04 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 7.73
(dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 3.38−3.31 (m, 2 H), 2.52−2.42
(m, 2 H), 2.21−2.12 (m, 2 H), 1.97−1.90 (m, 4 H), 1.78 (sept, J = 6.7
Hz, 2 H), 0.86−0.84 (two d; not resolved, J = 6.7 Hz, 12 H). 13C{1H}
NMR (CDCl3, 101 MHz): δ 198.6, 134.3, 134.2, 128.4, 126.9, 47.4,
42.0, 29.1, 27.1, 22.7, 22.6. HRMS (EI) m/z: [M]+• calcd for
C22H28O2, 324.2084; found, 324.2092.
4.5.3. 2,3-Di-(3-cyclohexylpropyl)-1,4,4a,9a-tetrahydro-9,10-an-
thraquinone (30c). Colorless crystalline solid; yield: 3.04 g (6.60
mmol, 73%). Rf (silica gel, n-hexane/CH2Cl2 2:1): 0.22. mp 122−124
°C. 1H NMR (CDCl3, 400 MHz): δ 8.04 (dd, J1 = 5.5 Hz, J2 = 3.3 Hz,
2 H), 7.73 (dd, J1 = 5.6 Hz, J2 = 3.3 Hz, 2 H), 3.33 (br t, J = 4.2 Hz, 2
H), 2.52−2.38 (m, 2 H), 2.22−2.11 (m, 2 H), 1.96 (t, J = 7.8 Hz, 4
H), 1.76−1.61 (m, 12 H), 1.40−1.30 (m, 4 H), 1.18−1.05 (m, 9 H),
0.94−0.76 (m, 5 H). 13C{1H} NMR (CDCl3, 101 MHz): δ 198.6,
134.3, 134.2, 128.3, 127.0, 47.4, 37.7, 33.6, 33.5, 33.2, 28.8, 26.9, 26.6,
25.7. HRMS (EI) m/z: [M]+• calcd for C32H44O2, 460.3336; found,
460.3346.
4.5.4. 2,3-Di-(ethyl-2-(1-adamantyl))-1,4,4a,9a-tetrahydro-9,10-
anthraquinone (30d). This compound was synthesized by reaction of
impure diene 28d with an excess of 1,4-naphthoquinone using the
general procedure. Colorless crystalline solid; yield: 0.16 g (0.3
mmol). Rf (silica gel, n-hexane/CH2Cl2 2:1): 0.38. mp 113−118 °C.
1H NMR (CDCl3, 400 MHz): δ 8.04 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2
H), 7.73 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 3.33 (br t, 4.8 Hz, 2 H),
2.50−2.38 (m, 2 H), 2.19−2.09 (m, 2 H), 1.99−1.85 (m, 10 H), 1.70
(br d, J = 12.0 Hz, 6 H), 1.62 (br d, J = 12.0 Hz, 6 H), 1.48 (d, J = 2.3
Hz, 12 H), 1.17−1.04 (m, 4 H). 13C{1H} NMR (CDCl3, 101 MHz): δ
198.7, 134.3, 134.2, 128.4, 127.0, 47.5, 43.1, 42.5, 37.4, 32.5, 29.0,
28.9, 25.8. MS (EI) m/z (%): 536.4 (100) [M]+•, 518.4 (5), 373.2
(74), 355.2 (9), 210.0 (10), 135.1 (45), 93.1 (8). Alongside Diels−
Alder adduct 30d the oxidation products 30d-2H and 31d could be
isolated.
4.4.3. 2,3-Di-(3-cyclohexylpropyl)-buta-1,3-diene (28c). 3-Cyclo-
hexylpropylmagnesium bromide in THF was prepared from 1-bromo-
3-cyclohexylpropane (26) and Mg turnings in the usual manner.
Colorless oil; yield: 2.18 g (7.22 mmol, 54%). bp 122 °C/6 × 10−2
mbar. 1H NMR (CDCl3, 400 MHz): δ 5.03 (br s, 2 H), 4.90 (br s, 2
H), 2.19 (t, J = 7.6 Hz, 4 H), 1.74−1.59 (m, 12 H), 1.48−1.38 (m, 4
H), 1.22−1.16 (m, 10 H), 0.91−0.83 (m, 4 H). 13C{1H} NMR
(CDCl3, 101 MHz): δ 148.3, 111.4, 37.8, 37.5, 34.8, 33.6, 26.9, 26.6,
26.1. HRMS (EI) m/z: [M]+• calcd for C22H38, 302.2968; found,
302.2961.
4.4.4. 2,3-Di-(ethyl-2-(1-adamantyl))buta-1,3-diene (28d). 1 M
ZnCl2 and 1 M CuCN·2 LiCl solutions were prepared according to
published procedure using anhydrous THF which was degassed prior
to use.62 Mg turnings ground under an atmosphere of Ar (0.4 g, 16.4
mmol, 2 equiv) were suspended in THF (15 mL) and 1,2-
dibromoethane (0.82 mmol, 70 mL, 5 mol %) followed by TMSCl
(0.82 mmol, 0.1 mL, 5 mol %) was added. To this solution, ZnCl2 in
THF (18.1 mL, 18.1 mmol, 1.1 equiv) was added dropwise. After
complete addition, 1-(2-bromoethyl)adamantane (4 g, 16.5 mmol)
was added in portions and the reaction was stirred overnight at 70 °C
in an oil bath. After cooling to rt, the solution of the zinc reagent was
added dropwise to a CuCN·2 LiCl solution in THF (16.5 mL, 16.5
mmol, 1 equiv) at −50 °C and stirred for 20 min, followed by addition
of 25 (2.6 g, 6.6 mmol, 0.4 equiv) in THF (20 mL). The solution was
allowed to warm to rt overnight, sat. aq NH4Cl (100 mL) was added
and the aqueous phase was extracted with n-pentane (100 mL). The
organic phase was washed with water (3 × 50 mL), dried over
Na2SO4, and evaporated, leaving a colorless oil; yield: 3.12 g. As the
material is contaminated with unreacted bromide evident by the EI
mass spectra only the characteristic signals for the double bonds are
given. Additionally, the HR-EI mass spectrum confirms the proposed
sum formula of the product. 1H NMR (CDCl3, 400 MHz): δ 5.03 (br
s, 2 H), 4.91 (br s, 2 H). 13C{1H} NMR (CDCl3, 101 MHz): δ 149.1,
111.2. HRMS (EI) m/z: [M]+• calcd for C28H42, 378.3281; found,
378.3289.
4.5.5. 2,3-Di-(ethyl-2-(1-adamantyl))-1,4-dihydro-9,10-anthra-
quinone (30d-2H). Orange solid; yield: 0.33 g (0.61 mmol). Rf
1
(silica gel, n-hexane/CH2Cl2 2:1): 0.52. mp 256−262 °C. H NMR
4.4.5. 2,3-Di-neopentyl-buta-1,3-diene (28e). Neopentylmagnesi-
um bromide was prepared from neopentylbromide and Mg turnings in
the usual manner. The reaction was conducted following the general
procedure using 5.9 g (15 mmol) of ditosylate 25. Colorless oil; yield:
(CDCl3, 400 MHz): δ 8.09 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 7.70
(dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 3.19 (s, 4 H), 2.10−2.02 (m, 4 H),
1.98 (br s, 6 H), 1.73 (br d, J = 12.0 Hz, 6 H), 1.65 (br d, J = 11.8 Hz,
6 H), 1.53 (d, J = 2.2 Hz, 12 H), 1.21−1.12 (m, 4 H). 13C{1H} NMR
(CDCl3, 101 MHz): δ 184.7, 142.4, 133.6, 132.3, 127.0, 126.3, 43.1,
42.5, 37.4, 32.6, 29.5, 28.9, 25.3. MS (EI) m/z (%): 534.2 (2), 518.4
(2), 369.2 (76), 135.1 (100), 93.0 (21).
1
1.94 g (10 mmol, 67%). bp 92 °C/30 mbar. H NMR (CDCl3, 400
MHz): δ 5.14 (d, J = 2.6 Hz, 2 H), 4.73 (d, J = 2.6 Hz, 2 H), 2.15 (s, 4
H), 0.90 (s, 18 H). 13C{1H} NMR (CDCl3, 101 MHz): δ 150.0,
115.9, 47.3, 31.8, 30.0. MS (EI) m/z (%): 194.1 (3) [M]+•, 123.0
(16), 71.0 (7), 57.0 (100). The spectra are in agreement with
published data.56
4.5.6. 2,3-Di-(ethyl-2-(1-adamantyl))-9,10-anthraquinone (31d).
Orange solid; yield: 0.049 g (0.092 mmol). Rf (silica gel, n-hexane/
CH2Cl2 2:1): 0.42. mp 261−264 °C. 1H NMR (CDCl3, 400 MHz): δ
8.29 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 8.03 (s, 2 H), 7.77 (dd, J1 =
5.8 Hz, J2 = 3.3 Hz, 2 H), 2.73−2.66 (m, 4 H), 2.02 (br s, 6 H), 1.76
(br d, J = 12.2 Hz, 6 H), 1.68 (br d, J = 12.0 Hz, 6 H), 1.60 (d, J = 2.2
Hz, 12 H), 1.40−1.33 (m, 4 H). 13C{1H} NMR (CDCl3, 101 MHz): δ
183.5, 149.2, 134.0, 133.9, 131.5, 128.3, 127.2, 46.3, 42.6, 37.3, 32.9,
28.9, 26.5. HRMS (EI) m/z: [M]+• calcd for C38H44O2, 532.3336;
found, 532.3359.
4.5. General Procedure for the Synthesis of 2,3-Disubsti-
tuted 1,4,4a,9a-Tetrahydro-9,10-anthraquinone Derivates
(30a−e). A solution of 1,4-naphthoquinone (1.08 g, 6.83 mmol)
and the corresponding butadiene (6.92 mmol, 1.01 equiv) in EtOH
(15 mL) was refluxed overnight in an oil bath. After cooling to rt, the
flask was kept at −10 °C overnight. The solid was filtered off, washed
with ice cold EtOH (20 mL), and dried in oil pump vacuum to give a
light grey to brown solid. The products are of sufficient purity for the
next reaction step but can be further purified by flash chromatography
(silica gel, n-hexane/CH2Cl2 2:1) if necessary.
4.5.7. 2,3-Di-neopentyl-1,4,4a,9a-tetrahydro-9,10-anthraqui-
none (30e). To a mixture of anhydrous CH2Cl2 (110 mL) and
anhydrous THF (0.12 mL, 1.49 mmol), AlCl3 (0.1 g, 0.74 mmol) was
added all at once and the mixture was stirred for 15 min. 1,4-
Naphthoquinone (2.63 g, 15 mmol, 1.08 eq) was added and the
mixture was stirred for another 15 min, followed by addition of the
diene 28e (2.79 g, 14 mmol) in one portion. The resulting mixture
was stirred at reflux overnight using an oil bath as heat source. After
cooling, the solvent was removed under reduced pressure and the
black residue was purified by flash chromatography (silica gel, n-
hexane/CH2Cl2 2:1). Yellow solid; yield: 1.59 g (4.51 mmol, 31%). Rf
4.5.1. 2,3-Di-n-butyl-1,4,4a,9a-tetrahydro-9,10-anthraquinone
(30a). 2,3-Di-n-butyl-buta-1,3-diene (28a) (2.28 g, 13.69 mmol)
was used for this synthesis. Colorless solid; yield: 2.79 g (8.6 mmol,
1
64%). Rf (silica gel, n-hexane/CH2Cl2 2:1): 0.24. mp 81−84 °C. H
NMR (CDCl3, 400 MHz): δ 8.04 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H),
7.73 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 3.38−3.31 (m, 2 H), 2.52−
2.41 (m, 2 H), 2.22−2.12 (m, 2 H), 2.00 (t, J = 7.9 Hz, 4 H), 1.41−
1.23 (m, 8 H), 0.90 (t, J = 7.1 Hz, 6 H). 13C{1H} NMR (CDCl3, 101
MHz): δ 198.6, 134.3, 134.2, 128.2, 126.9, 47.4, 32.6, 30.7, 28.8, 22.9,
14.2. HRMS (EI) m/z: [M]+• calcd for C22H28O2, 324.2084; found,
324.2073.
1
(silica gel, n-hexane/CH2Cl2 2:1): 0.38. mp 91−94 °C. H NMR
(CDCl3, 400 MHz): δ 8.04 (dd, J1 = 5.8 Hz, J2 = 3.3 Hz, 2 H), 7.73
K
J. Org. Chem. XXXX, XXX, XXX−XXX