, 2004, 14(6), 304–306
O
O
O
HN
NH
HN
i
O
O
O
O
NH
NH
O
N
iii
H
O
7
minor (30%)
major (70%)
8
9
4
6
Scheme 2 Reagents and conditions: i, KCN, (NH4)2CO3, EtOH/H2O,
i
50–65 °C, 24 h, reflux.
C(8) (Figure 1). A comparable type of steric hindrance is
characteristic of unsuccessful application of this reagent when
applied to the premade thermochromic dianthraquinone com-
pound, which could act as an intelligent material. Since there
will inevitably be a very negative entropy of activation due to
the loss of translational freedom in preparation of correspond-
ing mono and dihydantoin 15 compounds (Figure 2).
+ by-products
HO COOH
HO H
2
3
H
17
O
10
H
14
ii
H
H
O
H
13
HN
N
12
H
H
N
15
NH
6
11
5
O
R3
H
4
R2
1
O
18
H
H
8
9
7
ii
H
R1
1
H
N
3
2
H
H
O
H
H
12 R1 = NO2, R2 = R3 = H
13 R1 = R2 = NO2, R3 = H
14 R1 = R3 = NO2, R2 = H
H
O
Figure 1 MINDO/3 model of 8 [shows steric hindrance of the carbonyl
group C(11)–O(18) in the presence of hydrogens attached to C(8)].
5
Scheme 1 Reagents and conditions: i, NH2CONH2, EtOH or HO(CH2)2OH,
NaOH, H2O, 2–24 h, reflux; ii, KCN, (NH4)2CO3, EtOH/H2O, 50–65 °C,
48 h, reflux; iii, KCN, (NH4)2CO3, EtOH/H2O, 50–65 °C, 12 h, reflux.
In contrast to the dianthraquinone, 6-methoxy-3,4-dihydro-
2H-naphthalene-1-one 10 with KCN, (NH4)2CO3 in the EtOH/
H2O solvent system led to the formation of racemic 11
(Scheme 3).¶
e.g., refluxing for 12–48 h and changing the solvent system such
as DMF/H2O and dioxane/H2O failed. In the other effort the
reaction of phenanthrene-9,10-dione 4 with KCN, (NH4)2CO3
in EtOH/H2O after 12 h reflux led to the synthesis of 1-H-1,3-
diazatriphenylene-2,4-dione 6 (Scheme 1).‡
This efficient and versatile reagent was used for the synthesis
of diastereoselective chiral 5,5-spirohydantoins 9 and 8 related
to 1,7,7-trimethylbicyclo[2,2,1]heptan-2-one [(+)-camphor] 7
(Scheme 2).§ Herein we report on a synthesis entry to new spiro-
hydantoins by employing KCN and (NH4)2CO3 in the EtOH/
H2O solvent system on (+)-camphor. The mixture of diastereo-
isomers 9 and 8 was obtained in 40% yield. The ratio of 9 to 8
was ~7:3. This is best ascertained by monitoring the total integral
for two characteristic methyl signals for each isomer. Thus, the
ratio of the combined integral for the peaks at d = 0.99 and 0.8
for 9 to the combined integral for the peaks at d = 0.85 and
0.79 for 8 was 7 to 3 by H NMR. The 13C NMR spectrum of
1
the recrystallised compound in [2H6]DMSO showed 24 peaks,
mp 260–265 °C (decomp.), [a]D20 = +166.6° (c 1.012, DMSO).
Examination of the MINDO/3 model of 8 and 9 indicated
more interactions for 8 in contrast to 9.15 These interactions are
predominantly accounted for the steric hindrance of the carbonyl
group C(11)–O(18) in the presence of hydrogen attached to
Figure 2 Dot surface model for thermochromic dianthraquinone 15
[points to an extremely negative entropy of activation (CS Chem 3D 5.0)].
§
Synthesis of hydantoins 8 and 9 from 1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-one [(+)-camphor]. The crude material was several times
recrystallised from 96% EtOH; 1.3 g (40%) of pure white needle crystals
of 8 and 9 were collected; mp 260–265 °C (decomp.), [a]D20 = +166.6°
(c 1.012, DMSO). The ratio of 8 to 9 was ~3:7. IR (KBr, n/cm–1): 3200
(m), 3050 (w), 2975 (m), 2925 (m), 1760 (s), 1710 (vs), 1400 (m).
‡
Synthesis of 1H-1,3-diazatriphenylene-2,4-dione 6. A comparable
procedure as used for 1 was applied, but the reaction mixture was
refluxed for 12 h. The crude material was purified by preprative TLC
and several times recrystallised from 96% EtOH; 1.7 g (57%) of pure
spangle crystals of 6 were collected; mp 188 °C. 1H NMR ([2H6]DMSO)
d: 12.31 (s, 1H), 11.56 (s, 1H), 8.65 (t, 2H, J 9.07 Hz), 7.98 (d, 1H,
J 7.84 Hz), 7.86 (d, 1H, J 7.86 Hz), 7.65 (d, 1H, J 7.27 Hz), 7.62 (d, 1H,
J 7.66), 7.57 (t, 1H, J 7.38), 7.52 (t, 1H, J 7.34 Hz), 3.4 (H2O), 2.4
(DMSO). 13C NMR ([2H6]DMSO) d: 155.09, 134.40, 127.57, 127.32,
127.07, 126.29, 125.83, 125.12, 123.83, 123.89, 122.05, 121.44, 119.73,
119.45, 119.00. IR (KBr, n/cm–1): 3270 (m), 3450 (w), 3150 (m), 3080
(m), 1750 (s), 1715 (s), 1610 (m).
1
For 8: H NMR ([2H6]DMSO) d: 10.74 (s, 1H), 8.13 (s, 1H), 2.05 (s,
1H), 1.81 (d, 1H, J 2.5 Hz), 1.79 (d, 2H, J 5 Hz), 1.66 (d, 2H, J 5 Hz),
1.55 (d, 1H, J 5 Hz), 0.85 (s, 6H), 0.79 (s, 3H). 13C NMR ([2H6]DMSO)
d: 179.18, 157.15, 58.68, 52.50, 46.76, 45.06, 40.41, 37.18, 36.36,
31.50, 25.95, 15.55.
1
For 9: H NMR ([2H6]DMSO) d: 10.74 (s, 1H), 8.0 (s, 1H), 2.07 (s,
1H), 1.815 (d, 1H, J 2.5 Hz), 1.76 (d, 2H, J 5 Hz), 1.72 (dd, 2H), 1.57
(d, 1H, J 5 Hz), 0.85 (s, 6H), 0.79 (s, 3H). 13C NMR ([2H6]DMSO) d:
179.44, 156.72, 56,78, 54.76, 48.49, 35.05, 26.50, 25.95, 25.01, 15.45,
two peaks are combined with DMSO signals.
Mendeleev Commun. 2004 305