Claisen rearrangement of allyloxyanthraquinones with silver/potassium iodide in acetic acid as a new and efficient reagent

Full text of DOI:10.1021/jo991674z

J . Org. Chem. 2000, 65, 2813-2815
2813
conditions (110 °C). First, we examined the effect of Ag/
KI on simple allyloxyanthraquinone under mild condi-
tions. When allyl ether 1 was heated with Ag/KI (1:1
equiv) in AcOH at 110 °C, the Claisen rearrangement
proceeded to furnish 8 in 97% yield after 30 min (Table
1).
Cla isen Rea r r a n gem en t of
Allyloxya n th r a qu in on es w ith Silver /
P ota ssiu m Iod id e in Acetic Acid a s a New
a n d Efficien t Rea gen t
Hashem Sharghi* and Ghasem Aghapour
As Table 1 also shows, the standard electrode potential
for the half-reaction AgX + e- h Ag + X- decreases with
decreasing solubility product constant (Ksp) of AgX.13
Therefore, the reducing ability of Ag/KX is favored as X-
changes from F- to I-, and an increase in the yield of
the rearranged product is expected when Ag/KI is used
as the reducing agent. It may be noted that only 0-10%
of 8 is formed on prolonged heating of an o-xylene
solution of 1 at 150 °C.14 It is very likely that Ag/KI
reduces the anthraquinone moiety to its electron-rich
hydroquinone state, thereby facilitating the rearrange-
ment in a manner a carbonium accelerates [3,3] sigma-
tropic rearrangement.15-16 The extension of this new
reagent to Claisen rearrangement of other allyloxyan-
thraquinones was also successful. Thus, Ag/KI rear-
ranged the allyloxyanthraquinones to 2-allyl-1-hydroxy-
anthraquinones. Several examples of Claisen rearrange-
ment of allyl ethers are shown in Table 2 and Scheme 1.
As seen in Table 2 and Scheme 1, the reaction of
allyloxyanthranquinones with Ag/KI affords 2-allyl-1-
hydroxyanthraquinones in high yields.
Most notably, reductive Claisen rearrangements of 1,4-
bisallyloxyanthraquinones can be carried out to give
singly or doubly rearranged products with remarkable
selectivity. Treatment of the bisallyloxyanthraquinone 2
under the above conditions gave only a low (17%) yield
of 18, the product of double Claisen rearrangement,
together with mono Claisen rearrangement product 10,
whose yield depended on the time of the reaction.
However, when the reaction was carried out with Ag/
KI (5 equiv each) for 90 min, the product of double
rearrangement (18) was obtained in 68% yield. When this
reaction was refluxed under air atmosphere for 16 h, the
desired 2,3-diallylanthraquinone (11) was obtained in
65% yield.
Department of Chemistry, College of Sciences, Shiraz
University, Shiraz 71454, Islamic Republic of Iran
Received October 26, 1999
In tr od u ction
Functionalized anthraquinones have received much
attention in recent years due to their industrial applica-
tions (e.g., textile dyestuff)1 and their use as antiinflam-
matory agents2 in the treatment of rheumatoid arthritis
and as functional starting units in total synthesis of
anthracycline antibiotics as anticancer drugs.3 Yet the
functionalization has been restricted to a narrow choice
of chemical transformations. This is largely due to
inertness of anthraquinone moieties to common electro-
philic substitution reactions. Reductive Claisen rear-
rangement of allyloxyanthraquinones3,4 has become a
standard method for the introduction of alkyl groups onto
the nucleus of anthraquinones.5,6 Reduction of the qui-
none functionality with sodium dithionite in a mixture
of N,N-dimethylformamide and water (1:1) as the pre-
ferred solvent3,4 activates anthraquinonyl ethers, giving
higher yields and thereby permitting rearrangement at
temperatures (50-105 °C) much lower than those re-
quired for thermal rearrangements.7,8 However, some
workers have found it necessary to reoxidize the primary
products and have encountered the loss of a methoxy
group para to a rearranging allyl group,6 and in some
cases the formation of anthracenone9 or side chain double
bond isomerization10 has been reported. In our hands,
problems with poor reproducibility have been experi-
enced, and in this paper, we wish to introduce silver/
potassium iodide (Ag/KI) in acetic acid as a new and
efficient reagent for the reductive Claisen rearrangement
of allyloxyanthraquinones.
In the case of the 1,8-diallyloxyanthraquinone 6, the
products and yields depended on the conditions used. The
highest yield of double rearrangement products (15) was
obtained when Ag/KI (2 equiv each) was used for 15 min.
Of special note is that no demethoxylation and reduction
of the carbonyl group occur with Ag/KI; for example,
p-methoxy allyl ether 3 afforded the expected product 12
in 70% in 45 min.
Resu lts a n d Discu ssion
We examined the title reaction for the use of Ag/KI and
found that Ag/KI in AcOH is also able to promote Claisen
rearrangement of allyloxyanthraquinones under mild
(1) Dauzonne, D.; Fourris, S. Tetrahedron 1993, 49, 8865.
(2) Friedmann, C. A. U.S. Patent 4,346,103, 1982.
(3) Boddy, I. K.; Boniface, P. J .; Cambie, R. C.; Craw, P. A.; Larsen,
D. S.; McDonald, H.; Rutledge, P. S.; Woodgate, P. D. Tetrahedron Lett.
1982, 23, 4407.
Con clu sion s
In summary, Ag/KI is introduced as a new and efficient
reagent in Claisen rearrangement of allyloxyanthraqui-
(4) Cambie, R. C.; Rutledge, P. S.; Woodgate, P. D. Aust. J . Chem.
1992, 45, 483.
(5) Cava, M. P.; Ahmed, Z.; Benfaremo, N.; Murphy, R. A.; Malley,
G. J . O., J r. Tetrahedron 1984, 40, 4767. Rao, J . A.; Cava, M. P. J .
Org. Chem. 1989, 54, 2751.
(11) Skoog, D. A.; West, D. M.; Holler, F. J . Fundamentals of
Analytical Chemistry, 5th ed.; Saunders College Pub.: New York, 1988.
(12) J u, Lurie, Handbook of Analytical Chemistry, Second Printing;
MIR Pub.: Moscow, 1978; p 76.
(6) Hauser, F. M.; Hawawasam, P. J . Org. Chem. 1988, 53, 4515.
(7) Cambie, R. C.; Huang, Z.-D.; Noall, W. I.; Rutledge, P. S.;
Woodgate, P. D. Aust. J . Chem. 1981, 34, 819.
(8) Cambie, R. C.; Dunlop, M. G.; Noall, W. I.; Rutledge, P. S.;
Woodgate, P. D. Aust. J . Chem. 1981, 34, 1079.
(13) Skoog, D. A.; West, D. M.; Holler, F. J . Fundamentals of
Analytical Chemistry, 5th ed.; Saunders College Pub.: New York, 1988;
p 298.
(14) Wong, C. M.; Singh, R.; Singh, K.; Lam, H. Y. P. Can. J . Chem.
1979, 57, 3304.
(9) Prinz, H.; Wiegrebe, W.; Muller, K. J . Org. Chem. 1996, 61, 2853.
(10) V. S. N. Murty, K.; Pal, R.; Datta, K.; Mal, D. Synth. Commun.
1994, 24(9), 1287.
(15) Denmark, S. E.; Harmata, M. A. J . Am. Chem. Soc. 1982, 104,
4972.
(16) Hine, J . J . Am. Chem. Soc. 1950, 72, 2438.
10.1021/jo991674z CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/04/2000

2814 J . Org. Chem., Vol. 65, No. 9, 2000
Notes
Ta ble 1. Cla isen Rea r r a n gem en t of
1-Allyloxya n th r a qu in on e (1) to
2-Allyl-1-h yd r oxya n th r a qu in on e (8) w ith Ag/KX in
Reflu xin g Acetic Acid
allyloxyanthraquinone derivatives, (d) work up is easy,
and (e) demethoxylation, isomerization of double bonds,
and reduction of carbonyl groups do not occur.
entry
X
time (min)
yield (%)
Ksp of AgX
E° a
Exp er im en ta l Section
1
2
3
4
F
240
150
45
5
10
95
97
b
1.82 × 10-10
5.2 × 10-13
8.3 × 10-17
+0.222
+0.073
-0.151
Elemental analyses were performed at the National Oil Co.
of Iran at Tehran Research Center.
Cl
Br
I
30
Gen er a l P r oced u r e for Red u ctive Cla isen Rea r r a n ge-
m en t of Allyloxya n th r a qu in on es w ith Ag/KI. To a solution
of allyloxyanthraquinone (1 mmol) in glacial acetic acid (15 mL)
are added silver powder (1-5 mmol) and potassium iodide (1-5
mmol). The mixture is heated at reflux until TLC shows the
reaction to be complete. Then, the reaction mixture is filtered,
and water (60 mL) is added to the filtrate. The precipitate is
removed by filtration and washed with water. If a precipitate
does not form, the mixture is extracted with dichloromethane.
a
Standard electrode potential for the half-reaction11 AgX + e-
h Ag + X- (X: Cl, Br, I). Solubility of AgF is 172 g/100 mL in
b
water.12
Ta ble 2. Red u ctive Cla isen Rea r r a n gem en t of
Allyloxya n th r a qu in on es
substrate
ratioa
time (min)
product
yield (%)
The organic phase is washed with water, saturated NaHCO3
and saturated NaCl and dried over sodium sulfate. After
evaporation of solvent, a precipitate is obtained.
Data for compounds 8, 10, and 11 have been published
previously in refs 16, 8, and 7, respectively.
1,4-Dih ydr oxy-2-(pr op-2′-en yl)an th r aqu in on e (9): red crys-
tals (from acetone); mp 139-140 °C; 1H NMR (CDCl3, 250 MHz)
δ 3.40-3.43 (d, 2H, J ) 7.5 Hz), 5.09-5.15 (m, 2H), 5.84-6.01
(m, 1H), 7.08 (s, 1H), 7.71-7.75 (m, 2H), 8.22-8.26 (m, 2H),
12.83 (s, 1H), 13.27 (s, 1H) ppm; IR (KBr) 3670-3200 (b), 1630
(m) cm-1; UV (MeOH) λmax (log ꢀ), 206.7 (4.18), 225.1 (4.05), 251.4
(4.28), 273.1(3.86), 482 (3.54) nm; MS m/e 280 (M, 100%), 262
(M - H2O, 61%). Anal. Calcd for C17H12O4: C, 72.86; H, 4.28.
Found: C, 72.65; H, 4.3%.
,
1
2
2
2
3
4
4
5
6
6
7
1:1:1
1:1:1
1:3:3
1:3:3b
1:1:1
1:5:5
1:5:5b
1:1:1
1:1:1
1:2:2
1:1:1
30
15
90
960
45
45
1020
40
20
15
45
8
10
18
11
12
17
9
13
14
15
16
97
70
68
65
70
65
60
90
60
95
97
a
b
AQ:Ag:KI (equiv). When the starting material was finished
(90 and 45 min for compounds 2 and 3, respectively), the reaction
mixture was filtered, and the filtrate was heated at 85-90 °C until
the final product was completed.
1-Hydr oxy-4-m eth oxy-2-(pr op-2′-en yl)an th r aqu in on e (12):
1
red solid; mp 118-119 °C; H NMR (CDCl3, 250 MHz) δ 3.50-
3.53 (d, 2H, J ) 7.5 Hz), 3.96 (s, 3H), 5.15-5.22 (m, 2H), 5.97-
6.07(m, 1H), 7.21-7.24 (s, 1H), 7.70-7.77 (m, 2H), 8.23 (m, 2H),
13.38-13.41 (s, 1H) ppm; IR (KBr) 3640-3350 (b), 1660 (s), 1633
(m) cm-1 ; UV (MeOH) λmax (log ꢀ), 205.2 (4.44), 205.8 (4.42),
230.7 (4.48), 251.7 (4.64), 278.5 (4.14), 317.8 (3.54), 460 (4.20)
nm; MS m/e 294 (M, 100%), 265 (M - CHO, 34.4%). Anal. Calcd
for C18H14O4: C, 73.47; H, 4.76. Found: C,73.1; H, 4.55%.
1,8-Dih yd r oxy-2-(p r op -2′-en yl)a n th r a qu in on e (13): yel-
low needles (from ethanol); mp 131-132 °C; 1H NMR (CDCl3) δ
3.45 (d, 2H, J ) 6 Hz), 4.8-6.4 (m, 3H),7.0-7.8 (m, 5H), 12.0 (s,
1H), 12.35 (s, 1H) ppm; IR (KBr) 3100-2800 (b), 1670 (s), 1620
(s),1600 (s) cm-1; UV (MeOH) λmax (log ꢀ), 202 (4.36), 227 (4.63),
255 (4.38), 286 (3.99), 430.5 (4.05) nm; MS m/e 280 (M, 100%).
Anal. Calcd for C17H12O4: C, 72.86; H, 4.28. Found: C,73.0; H,
5.0%.
Sch em e 1
1-H y d r o x y -2-(p r o p -2′-e n y l)-8-(p r o p -2′-e n y lo x y )a n -
th r a qu in on e (14): yellow solid; mp 113-114 °C; 1H NMR
(CDCl3, 250 MHz) δ 3.50-3.52 (d, 2H, J ) 5.0 Hz), 4.77-4.78
(d, 2H, J ) 2.5 Hz), 5.10-5.17 (m, 2H), 5.41 (dd, 1H), 5.70-
5.71 (dd, 1H), 6.0 (m, 2H), 7.29-7.95 (m, 5H), 13.4 (s, 1H) ppm;
IR (KBr) 3600-3100 (b), 3100-2800 (b), 1640 (s), 1610 (m) cm-1
;
UV (MeOH) λmax (log ꢀ), 204.4 (4.314), 227 (4.98), 258.3 (4.311),
415 (3.84) nm; MS m/e 320 (M, 25.6%), 291 (M - CHO, 24.2%),
279 (M - C3H5, 70.6%). Anal. Calcd for C20H16O4: C, 75.0; H,
5.0. Found: C, 74.8; H, 4.75%.
1,8-Dih yd r oxy-2,7-bis(p r op -2′-en yl)a n th r a qu in on e (15):
yellow needles; mp 150-151 °C; 1H NMR (CDCl3) δ 3.35 (d, 4H,
J ) 6 Hz), 4.7-6.3 (m, 6H), 7.3 (d, 2H, J ) 8 Hz), 7.55 (d, 2H,
J ) 8 Hz), 12.3 (s, 2H) ppm; IR (KBr) 3600-3300 (b), 3100-
2900 (b), 1670 (s), 1640 (s) cm-1; UV (MeOH) λmax (log ꢀ), 202
(3.97), 229 (4.25), 260 (4.07), 291 (3.58), 435 (3.69) nm; MS m/e
320 (M, 100%), 287 (M - HO2, 13.2%), 265 (M - C3H3O, 13.4%).
Anal. Calcd for C20H16O4: C, 75.0; H, 5.0. Found: C, 75.2; H,
5.1%.
1-H yd r oxy-8-m et h oxy-2-(p r op -2′-en yl)a n t h r a q u in on e
1
(16): yellow needles (from acetone); mp 158-159 °C; H NMR
(CDCl3, 250 MHz) δ 3.54-3.57 (d, 2H, J ) 7.5 Hz), 4.11 (s, 1H),
5.15-5.21 (m, 2H), 6.00-6.14 (m, 1H), 7.29-8.02 (m, 5H), 13.36
(s, 1H) ppm; IR (KBr) 3640-3200 (b), 3120-2800 (b), 1670 (m),
1640 (s) cm-1; UV (MeOH) λmax (log ꢀ), 225 (4.72), 257.4 (4.48),
417.8 (3.95) nm; MS m/e 294 (M, 86.8%), 279 (M - CH3, 100%).
Anal. Calcd for C18H14O4: C, 73.47; H, 4.76. Found: C,73.2; H,
4.6%.
nones. The present method has the following advantages:
(a) the reagent is readily available and safe to handle,
(b) the procedure is simple, (c) the reaction times are
short that can be performed with a wide range of

Notes
J . Org. Chem., Vol. 65, No. 9, 2000 2815
2-(P r op -2′-en yl)-9,10-d ih yd r oxy-2,3-d ih yd r o-1,4-a n th r a -
(m, 4H), 2.97-3.2 (m, 2H), 5.07-5.20 (m, 4H), 5.71-5.82 (m,
2H), 7.76-7.81 (m, 2H), 8.45-8.51 (m, 2H), 13.65 (s, 2H) ppm;
IR (KBr) 3630-3300 (b), 3100-2800 (b), 1645 (s) cm-1; UV
(MeOH) λmax, 203.4, 238.7, 258.6, 277.3, 399.2, 418.4. Anal. Calcd
for C20H18O4: C, 74.53; H, 5.59. Found: C, 74.3; H, 5.35%.
1
cen d ion e (17): yellow solid; mp 91-92 °C; H NMR (CDCl3) δ
2.33-2.63 (m, 2H), 2.80-3.05 (m, 3H), 5.03-5.1 (m, 2H), 5.67-
5.74 (m, 1H), 7.64-7.70 (m, 2H) 8.31-8.34 (m, 2H), 13.42 (s,
1H), 13.48 (s, 1H) ppm; IR (KBr) 3100-2800 (b), 1635 (s) cm-1
;
UV (MeOH) λmax (log ꢀ), 232.6 (4.217), 235.5 (4.216), 244.9 (4.19),
273.2 (4.00), 273.1 (4.01), 283.5 (4.03), 286.4 (4.05), 398.1 (4.08),
416.5 (4.06) nm; MS m/e 282 (M, 62.6%), 241 (M - C3H5, 100%).
Anal. Calcd for C17H14O4: C, 72.34; H, 4.96. Found: C, 72.25;
H, 4.75%.
Ack n ow led gm en t. We gratefully acknowledge the
support of this work by the Shiraz University Research
Council.
2,3-Bis(p r op -2′-en yl)-9,10-d ih yd r oxy-2,3-d ih yd r o-1,4-a n -
th r a cen d ion e (18): yellow solid; 1H NMR (CDCl3) δ 2.47-2.52
J O991674Z