intermediate. The cyclization process might occur in either
a stepwise or a concerted manner. The strained intermedi-
ate was highly unstable and collapsed to release CO2 to
give the desired diaryldibenzodiazocine. This reaction was
promoted under acidic conditions, in which the proton-
ation of a carbonyl group might facilitate the cyclization. In
the presence of water, the aminobenzophenone formation
process competed with this process. Diluted acidic condi-
tions are also unfavorable for diazocine synthesis.
Table 2. Scope of Diaryldibenzo[b,f][1,5]diazocines Synthesis
This hypothesis was supported by some experimental
evidences. First, the condensation mechanism could be ruled
out because it would require 2-aminobenzophenone as the
intermediate. As mentioned previously, the failure to con-
vert 2-aminobenzophenone to the corresponding diazocine
under the reaction conditions eliminates this pathway.
Second, under water-free conditions, we did observe the
formation of CO2 during the reaction, which was followed
immediately by the diazocine formation (see Supporting
Information) and supported the mechanism we proposed.
The mechanism of a [2 þ 2] cyclization was also sup-
ported by literature precedent. It was reported that phenyl
isocyanate underwent [2 þ 2] cyclization with excess DMF
to form 4-(dimethylamino)-3-phenyl-1,3-oxazetidin-2-one
which collapsed and released CO2 to form the imine bond.11
Although 1,3-oxazetidin-2-one intermediates are generally
highly unstable, a stable 1,3-oxazetidin-2-one was isolated
whenmethyl isocyanate was reacted witha highly electron-
deficient ketone.12 Furthermore, the reaction was promoted
either in acidic conditions or in the presence of a fluoride
anion,12 which shows some similarity to our synthesis. A
reaction between phthaldehyde and phenyl isocyanate was
also reported, which was postulated to go through a 1,3-
oxazetidin-2-one intermediate to give N-phenyl-phtha-
limidine.13 1,3-Oxazetidin-2-one was also prepared by
other pathways, and its release of CO2 to form an imine
bond at an elevated temperature was confirmed.14
temp
entry
2
R
(°C)
solvent
AcOH
3a
1
2
3
4
5
6
7
a
b
c
d
e
f
4-Br
4-I
80
80
80
80
80
80
80
77%
71%
74%
83%
86%
AcOH
H
AcOH
4-Me
4-OMe
4-Cl
3-NO2
AcOH
AcOH
TFA (AcOH)
TFA (AcOH)
70% (60%)
78% (30%)
g
a Isolated yield.
The influence of the substituents on the phenyl ring on the
efficiency of cyclization was investigated, as shown in Table 2.
Although using TFA as the solvent generally gave better yields,
we used AcOH as the solvent in most cases for considerations
of toxicity and economic reasons. Phenyl rings bearing elec-
tron-donating groups such as methyl and methoxy groups gave
better yields (Table 2, entries 4, 5). More electronegative groups
such as Cl and NO2 led to lower yields when the reactions were
performed in AcOH, but the yields were increased (Table 2,
entries 6, 7) when the solvent was switched to TFA .
Given that the 2-aminobenzophenone could not afford
the corresponding dibenzodiazocine under the reaction
conditions chosen, a different mechanism was proposed,
as shown in Scheme 3. We assumed that the first step was
the Curtius rearrangement, which expelled 1 equiv of N2
and gave the corresponding isocyanate. In the absence of
suitable nucleophiles such as water to attack, the resulting
isocyanate underwent an intermolecular [2 þ 2] cyclization
under acidic conditions with the ketone moiety of another
molecule to give a highly strained 1,3-oxazetidin-2-one
In summary, a rapid and efficient method for the synthe-
sis of diaryldibenzo[b,f][1,5]diazocines was developed.
Starting from easily available 2-benzoylbenzoic acid, sym-
metric diazocines could be prepared in two steps in good
yield. The mechanism of the key reaction is plausibly an
unprecedented intermolecular [2 þ 2] cyclization between
an isocyanate and ketone moieties. We are currently
exploring further applications of this reaction.
Scheme 3. Plausible Mechanism for the Synthesis of
Diaryldibenzo[b,f][1,5]diazocines
Acknowledgment. This project is supported by the “100
Talents” program from the Chinese Academy of Sciences.
Supporting Information Available. General procedures
for the synthesis of diazocines and its precursors, char-
acterization, and spectroscopic data of the key com-
pounds are included. This material is available free of
(11) Weiner, M. J. Org. Chem. 1960, 25, 2245.
(12) Shozda, R. J. J. Org. Chem. 1967, 32, 2960.
(13) Yamamoto, I.; Tabo, Y.; Gotoh, H.; Minami, T.; Ohshiro, Y.;
Agawa, T. Tetrahedron Lett. 1971, 12, 2295.
(14) Momot, V. V.; Samarai, L. I.; Bodnarchuk, N. D. Synthesis
1980, 571.
Org. Lett., Vol. 13, No. 4, 2011
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