Novel synthesis of oxadiazinone and oxadiazepinone derivatives by ring expansion of diaziridinone

Article abstract of DOI:10.3987/COM-99-S66

Treatment of N, N'-di-tert-butyldiaziridinone with α-hydroxy ketones in the presence of a catalytic amount of BF₃·OEt₂ gave carbazate derivatives in excellent yields. Acid-catalyzed recyclization of these compounds easily proceeded to give oxadiazinone derivatives. The reaction was applicable to the synthesis of oxadiazepinone derivatives and also to one-pot process.

Full text of DOI:10.3987/COM-99-S66

HETEROCYCLES, Vol. 52, No.2, 2000, pp. 541 – 544, Received, 30th April, 1999ꢀꢀꢀ
NOVEL SYNTHESIS OF OXADIAZINONE AND OXADIAZEPINONE
#
DERIVATIVES BY RING EXPANSION OF DIAZIRIDINONE
a
Mitsuo Komatsu,* Norio Sakai, Akira Hakotani, Satoshi Minakata, and
a
a
a
b
Yoshiki Ohshiro
a
ꢀ
Department of Applied Chemistry, Faculty of Engineering, Osaka University
Yamadaoka 2-1, Suita, Osaka 565-0871, Japan
b
Research Institute for Science and Technology, Kinki University
Kowakae 3-4-1, Higashi-Osaka, Osaka 577-0818, Japan
Abstract-Treatment of N, N'-di-tert-butyldiaziridinone with ꢀ-hydroxy ketones in
the presence of a catalytic amount of BF •OEt gave carbazate derivatives in
3
2
excellent yields. Acid-catalyzed recyclization of these compounds easily proceeded
to give oxadiazinone derivatives. The reaction was applicable to the synthesis of
oxadiazepinone derivatives and also to one-pot process.
Three-membered heterocycles have served as potential building blocks for the synthesis of numerous types
of heterocycles.1 Among these small rings, diaziridinones2 show unique ring opening reactivity because of
their highly strained three-membered structures which consist of a carbonyl carbon and two nitrogen
atoms.1-3 Previously, we reported the ring enlargement reactions of N, N'-di-tert-butyldiaziridinone (1)
with anionic species, which are metalated isocyanides,4a ꢀ-metalated nitriles,4b metalated active methylene
compounds,4c and 1-sodio-2-formylpyrrole,4d via ring opening and recyclization. Although diaziridinone
(1) bears two tert-butyl groups on nitrogen atoms to stabilize the three-membered ring, the substituents on
products can be readily removed under acidic conditions, and hence diaziridinone (1) can be regarded as the
non-substituted diaziridinone. On the other hand, we have already showed the ring expansion of 1 with
benzonitrile in the presence of Lewis acid.5 Thus, this property forced us to investigate the reaction of
diaziridinone with other neutral neucleophiles. Here we report the acid-catalyzed ring opening and
subsequent recyclization reactions of diaziridinone (1) with several alcohols having a carbonyl group.
tBu
N
O
O
O
acid (0.2 equiv)
O
HO
R2
R2
+
tBu
N
tBuN
NBut
R1
H
R1
2a-c (1 equiv)
O
1 (1 equiv)
3a-c
Acid-catalyzed ring opening reactions of N, N'-di-tert-butyldiaziridinone (1) with ꢀ-hydroxy ketones (2a-c)
are summarized in Table1. Treatment of 1 with hydroxyacetone (2a) in the presence of a catalytic amount
#
Dedicated to Professor Teruaki Mukaiyama on the occasion of his 73rd birthday.

of BF •OEt in CHCl at 0 °C for 0.5 h gave acetylmethyl carbazate (3a) in 92% yield. The reaction
3
2
3
proceeded with high yields in any of the other solvents, such as THF, Et O or PhMe. Although p-
2
toluenesulfonic acid (PTS) did not catalyze the reaction at 0 °C, the desired product was obtained in 81%
yield by raising the reaction temperature to 60 °C. 2-Hydroxyacetophenone (2b) also reacted with 1 in
good yield to give a benzoyl derivative (3b). The reaction was applicable to a hydroxy ester having a
secondary hydroxy group. The substituents on the carbonyl group of 2 did not prevent the formation of 3.
Table 1. Acid-Catalyzed Ring Opening Reactions of 1 with 2a-c
R1
R2
solv.
temp. (°C)
time (h)
acid
yield (%)
H
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Ph (2b)
OEt (2c)
BF3 • OEt2
BF3 • OEt2
BF3 • OEt2
BF3 • OEt2
PTSa)
CHCl3
THF
0
0
0.5
0.5
0.5
0.5
0.5
1
92 (3a)
89 (3a)
88 (3a)
90 (3a)
0 (3a)
H
H
Et2O
0
H
PhMe
PhMe
CHCl3
CHCl3
CHCl3
0
H
0
H
PTS
60
0
81 (3a)
90 (3b)
90 (3c)
H
BF3 • OEt2
BF3 • OEt2
0.5
0.5
Me
0
a) p-toluenesulfonic acid.
Since no cyclic product was formed under the above mentioned conditions, recyclizations of isolated 3
were examined under heating in the presence of acid catalysts. When 3a was treated with a catalytic
amount of PTS in benzene at 80 °C, oxadiazinone derivatives (4a and 5a) were obtained. The position of
tert-butyl group on 4a was confirmed by existence of nOe between methyl and tert-butyl groups. While
BF •OEt was found to be a good catalyst for the recyclization of 3b to 4b, the recyclization of 3c did not
3
2
proceed under these conditions.
O
O
HN
tBuN
O
HN
tBu
O
for 3a: PTS (0.3 equiv), PhH, 80 °C, 30 h
for 3b: BF3•OEt2 (0.3 equiv), CHCl3, 60 °C, 20 h
3
+
N
R2
R2
OH
4a: 44%
4b: 59%*
5a: 2%
0%
* recovery of 3b: 30%
One-pot ring expansion reactions were studied because both the ring opening and recyclization reactions
proceeded under the same conditions using acid catalysts except for the factor of the temperature. When the
reaction of 1 with 2a was carried out under the following conditions, the cyclic products (4a and 5a) were

obtained. The hydroxy ketone (2b) also reacted with 1 to give the corresponding oxadiazinone (4b) in
good yield, as well as the non-cyclized product (3b).
BF3•OEt2 (0.5 equiv)
+
+
4a: 20% + 5a: 14%
4b: 57% + 3b: 13%
1
1
2a
2b
CHCl3, 0 °C, 30 min
reflux, 20 h
Then, ꢀ-hydroxy ketones were employed in the present reaction with the intention of obtaining seven-
membered heterocycles. Since acetophenone is readily converted into ꢀ-hydroxy ketone by aldol
condensation under acidic conditions, the reaction of 1 with acetophenone (6) in the presence of BF •OEt
3
2
gave an expected oxadiazepinone derivative (7) in one-pot process.
O
Me
O
Me
Ph
O
O
BF3•OEt2 (1 equiv)
tBu
Ph
N
N
+
+
1
PhH, reflux, 1.5 h
Ph
Me
Ph
Ph
7: 28%
6
8: 45%
Furthermore, salicylaldehyde was used as a substrate to synthesize a bicyclic seven-membered heterocycle.
Although the reaction of salicylaldehyde (9) with 1 gave a complicated mixture under the acidic conditions,
treatment of 9 with an equimolar amount of NaH followed by addition of 1 afforded the ring opening
product (10) in 41% yield. Subsequently, isolated 10 was heated in the presence of BF •OEt (0.3 equiv)
3
2
to give benzoxadiazepinone (11) in 53% yield.
tBu
N
O
OH
NH
tBu
NaH (1 equiv)
1
O
DMF, 0 °C, 10 min
100 °C, 24 h
CHO
CHO
10: 41%
9
O
O
BF3•OEt2 (0.3 equiv)
CHCl3, reflux, 20 h
tBu
N
N
11: 53%

In summary, we have demonstrated here a novel synthesis of oxadiazinones via carbazate derivatives
prepared effectively by the reaction of N, N'-di-tert-butyldiaziridinone with ꢀ-hydroxy ketones. The
present reactions are applicable to one-pot process and also to the synthesis of oxadiazepinone derivatives
by employing acetophenone and salicylaldehyde as a ꢁ-hydroxy carbonyl compound or its precursor. The
reactions of 1 with various types of hydroxy and mercapto ketones are under investigation.
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1
6. Selected spectroscopic data for 4a: IR (neat) 3300, 1762, 1670, 1132 cm-1; H-NMR (270 MHz,
CDCl3) ꢂ 1.17 (s, 9H), 1.99 (d, J = 1.7 Hz, 3H), 4.08 (br s, 1H), 6.48 (q, J = 1.7 Hz, 1H); 13C-
+
NMR (67.8 MHz, CDCl3) ꢂ 8.4, 27.9, 56.3, 121.2, 126.9, 156.5; EI-MS m/z 170 (M , 28), 114
+ t
M - Bu, 100). 4b: IR (neat) 3308, 3020, 2980, 1758, 1666 cm-1; 1H-NMR (270 MHz, CDCl3) ꢂ
1.00 (s, 9H), 4.40 (br s, 1H), 6.85 (s, 1H), 7.33-7.73 (m, 5H); 13C-NMR (67.8 MHz, CDCl3) ꢂ
+
27.9, 57.2, 122.0, 127.2, 127.9, 128.2, 128.8, 130.5, 156.2; EI-MS m/z 232 (M+, 24), 176 (M -
t
Bu, 100). 7: IR (nujol) 1750, 1570 cm-1; 1H-NMR (90 MHz, CDCl3) ꢂ 1.19 (s, 9H), 1.30 (s, 3H),
+
5.32 (d, J = 1.0 Hz, 1H), 5.37 (d, J = 1.0 Hz, 1H), 7.22-7.80 (m, 10H); EI-MS m/z 336 (M ). 11:
IR (neat) 2980, 1732, 1658 cm-1; 1H-NMR (270 MHz, CDCl3) ꢂ 1.43 (s, 9H), 7.09-7.68 (m, 4H),
+
+ t
8.25 (s, 1H); EI-MS m/z 218 (M , 29), 162 (M - Bu, 100).