Selective Synthesis of Novel Cyclic Phenylazomethine Trimers

Article abstract of DOI:10.1021/jo000509c

Novel cyclic phenylazomethine trimers (CPAs) were synthesized in a one-step dehydration of the 4-aminobenzophenone derivatives in the presence of TiCl₄ or p-toluenesulfonic acid (PTS). The CPAs were isolated in over 90% yield under nondilute co

Full text of DOI:10.1021/jo000509c

5680
J . Org. Chem. 2000, 65, 5680-5684
Selective Syn th esis of Novel Cyclic P h en yla zom eth in e Tr im er s
Masayoshi Higuchi, Atsushi Kimoto, Satoshi Shiki, and Kimihisa Yamamoto*
Department of Chemistry, Faculty of Science & Technology, Keio University, Yokohama 223-8522, J apan
yamamoto@chem.keio.ac.jp
Received April 4, 2000
Novel cyclic phenylazomethine trimers (CPAs) were synthesized in a one-step dehydration of the
4-aminobenzophenone derivatives in the presence of TiCl4 or p-toluenesulfonic acid (PTS). The CPAs
were isolated in over 90% yield under nondilute conditions. When using TiCl4 as the dehydration
agent, the induction of bulky substituents at the R-position of the substrate enhanced the yields of
the CPAs. On the other hand, PTS served as an effective catalyst for the synthesis of the phenyl-
substituted CPA. This different reactivity between TiCl4 and PTS depends on the dehydration
mechanism being dominated by a kinetic process or thermodynamic one. The obtained CPAs were
confirmed by NMR, UV-vis spectra, and MM2 calculation to have only a Z conformation and a
nonconjugated structure compared to the linear oligophenylazomethines (OPAs) and the aniline-
capped OPAs (OPA’s).
In tr od u ction
Herein, we report the synthesis of novel cyclic mol-
ecules with phenylazomethine backbones, cyclic pheny-
lazomethines (CPAs),6 which have an alternate structure
of phenylene and a CdN bond as compared to the
structure of the linear oligophenylazomethines (OPAs)
and the aniline-capped OPAs (OPA’s). A polyphenyla-
zomethine chain with the alternating structure of a
phenylene ring and a CdN bond should be a thermo-
stable aromatic polymer and have electronic functionality
because the structure is analogous to poly(phenylene
vinylene), which is an important conductive polymer.7 We
have succeeded in the selective synthesis of CPAs with
a high yield using TiCl4 or PTS.
There has been considerable interest in aromatic
macrocyclic oligomers that can be utilized as reactive
monomers in the ring-opening polymerization to give
linear polyaromatics with high molecular weight and
high purity, which are used as thermostable engineering
plastics. The thermal polymerization of cyclic thiophe-
nylene oligomers,1 the metathesis polymerization of cyclic
olefins,2 and the anionic polymerization of cyclic poly-
carbonates are examples of such.3 Most of the preparative
methods for these cyclic aromatic compounds result in
not only low yields but also in the formation of a mixture
of cyclic oligomers with different numbers of repeating
units along with linear oligomers.4 Until now, cyclic
compounds were synthesized under hyperdiluted condi-
tions, and there have been few reports about the highly
selective preparation of a discrete cyclic aromatic in a
one-step reaction.5 The convenient and efficient prepara-
tion of a cyclic oligomer potentially leads to a new reactive
monomer as a raw material for high performance poly-
mers.
Resu lts a n d Discu ssion
Syn th esis of Cyclic P h en yla zom eth in es (CP As).
In general, the dehydration of amines with aldehydes
efficiently takes place in the presence of p-toluenesulfonic
acid (PTS) as the catalyst, whereas the dehydration of
aromatic amines with aromatic ketones proceeded very
slowly (Scheme 1, Table 1, Run 1).8 Instead of PTS, TiCl4
is effective as a Lewis acid and as a dehydration agent
(Run 2). In the presence of TiCl4, the dehydration of 4′-
aminoacetophenone gave the corresponding polymer and
no cyclic trimer (Scheme 2, Table 2, Run 1). However,
the novel cyclic (R-phenyl)phenylazomethine trimer (CPA-
a) was obtained in a 20% yield under nondilute conditions
([monomer] ) 0.1 M) by the dehydration of 4-aminoben-
(1) (a) Wang, Y.; Chen, K. P.; Hay, A. S. Macromolecules 1995, 28,
6371. (b) Wang, Y.; Hay, A. S. Macromolecules 1996, 29, 5050. (c) Wang,
Y.; Hay, A. S. Macromolecules 1997, 30, 182. (d) Tsuchida, E.;
Miyatake, K.; Yamamoto, K.; Hay, A. S. Macromolecules 1998, 31,
646(29). (a) France, M. B.; Feldman, J .; Grubbs, R. H. J . Chem. Soc.,
Chem. Commun. 1994, 1307. (b) Hafner, A.; Mu¨hlebach, A.; van der
Schaaf, P. A. Angew. Chem., Int. Ed. Engl. 1997, 36, 2121.
(3) (a) Brunelle, D. J .; Krabbenhoft, H. O.; Bonauto, D. K. Macromol.
Symp. 1994, 77, 117. (b) J iang, H.; Chen, T.; Xu, J . Macromolecules
1997, 30, 2839. (c) Teasley. M. F.; Wu, D. Q.; Harlow, R. L. Macro-
molecules 1998, 31, 2064.
(4) (a) Memeger, W., J r.; Lazar, J .; Ovenall, D.; Leach, R. A.
Macromolecules 1993, 26, 3476 (cyclic aramids). (b) Chen, K. P.; Wang,
Y.; Hay. A, S. Macromolecules 1995, 28, 653 (cyclic aryl ether ketones).
(c) Chan, K. P.; Wang, Y.-F.; Hay, A. S.; Hronowski, X. L.; Cotter, R.
J . Macromolecules 1995, 28, 6705 (cyclic aryl ether ketones). (d) Ding,
Y.; Hay, A. S. Macromolecules 1996, 29, 6386 (cyclic aromatic disul-
fides). (e) J iang, H.; Liu, T.; Zhang, H.; Chen, T.; Mo, Z. Polymer 1996,
37, 3427 (cyclic aryl carbonates). (f) Colquhoun, H. M.; Lewis, D. F.;
Fairman, R. A.; Baxter, I.; Williams, D. J . J . Mater. Chem. 1997, 7, 1
(cyclic aryl thioether ketones). (g) Wang, J .; Chen, C.; Xun, X.; Wang,
S.; Wu, Z. J . Polym. Sci. A: Polym. Chem. 1999, 37, 1957 (cyclic aryl
ether ketones).
(6) Reported cyclic phenylazomethines: (a) Taylor, L. T.; Vergez,
S. C.; Busch, D. H. J . Am. Chem. Soc. 1966, 88, 3170. (b) Williams, P.
A.; Ellzey, K. A.; Padias, A. B.; Hall, H. K., J r. Macromolecules 1993,
26, 5820.
(7) (a) J in, J .; Park, C.; Shim, H. Macromolecules 1993, 26, 1799.
(b) J in, J .; Lee, Y.; Shim, H. Macromolecules 1993, 26, 1805. (c) Gurge,
R. M.; Sarker, A.; Lahti, P. M.; Hu. B.; Karasz, F. E. Macromolecules
1996, 29, 4287. (d) Lutsen, L.; Adriaensens, P.; Becker, H.; Van
Breemen, A. J .; Vanderzande, D.; Gelan, J . Macromolecules 1999, 32,
6517. (e) Brabec, C. J .; Padinger, F.; Sariciftci, N. S.; Hummelen, J . C.
J . Appl. Phys. 1999, 85, 6866.
(8) (a) Trost, B. M., Fleming, I., Eds. Comprehensive Organic
Synthesis; 1991; Vol. 6, p 705. (b) Weingarten, H.; Chupp, J . P.; White,
W. A. J . Org. Chem. 1967, 32, 3246. (c) White, W. A.; Weingarten, H.
ibid 1967, 32, 213.
(5) (a) Miyatake, K.; Yokoi, Y.; Yamamoto, K.; Tsuchida, E.; Hay,
A. S. Macromolecules 1997, 30, 4502. (b) Higuchi, M.; Yamamoto, K.
Org. Lett. 1999, 1, 1881.
10.1021/jo000509c CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/10/2000

Novel Cyclic Phenylazomethine Trimers
J . Org. Chem., Vol. 65, No. 18, 2000 5681
Sch em e 1. Syn th esis of a Mod el Com p ou n d 3
Sch em e 3. Syn th esis of OP As a n d OP A’s
Ta ble 1. Syn th esis of a Mod el Com p ou n d 3
Run
Acid (equiv)
Solvent
p-Xylene
Chlorobenzene
T °C
Yield, %
1
2
PTS (0.10)
TiCl4 (0.75)
140
125
19
91
Sch em e 2. Syn th esis of CP As
Ta ble 2. Syn th esis of CP A
yield of CPA (Run 7, 8). The other products were
confirmed by GPC to be the oligomers up to pentamer.
These different results between TiCl4 and PTS depend
on each specific dehydration mechanism as will be
described later.
Sp ectr oscop ic An a lysis of th e Azom eth in e Str u c-
tu r e. The linear oligophenylazomethines (OPAs) and the
aniline-capped OPAs (OPA’s) were synthesized as com-
parative compounds of CPAs (Schemes 3). The 13C NMR
spectra revealed that OPA3 and OPA2′ have 2 isomers
and OPA4 and OPA3′ have 4 isomers, respectively
(Figure 1). These isomers were caused by the E/ Z
conformation of the azomethine moiety. OPA3 has one
carbonyl and two azomethines, but two peaks attributed
to the carbonyl carbon at 203.04 and 202.85 ppm, and
four peaks attributed to the azomethine carbon at 187.20,
187.00, 183.83, and 183.80 ppm were observed in the 13C
NMR spectrum (Figure 1b). The formation ratio of the E
isomer with the Z one in the OPA3 was estimated to be
1:1, based on the area ratio of the two peaks attributed
to the carbonyl carbon. OPA4 has one carbonyl and three
azomethines, but the 13C NMR spectrum (Figure 1c)
shows four peaks attributed to the carbonyl carbon at
203.29, 203.11, 202.89, and 202.65 ppm and multiple
peaks attributed to the azomethine carbon. On the basis
of the integration ratio of each peak in the spectrum of
OPA4 (the pulse sequence is NNE), the formation ratio
of the four isomers was approximately estimated to be
9:6:3:1. Similar to OPA3 and OPA4, OPA2′ and OPA3′
showed multiple peaks corresponding to the isomeric
structures. In OPA2′ with two azomethines, four peaks
attributed to the azomethine carbon were observed at
168.96, 168.51, 168.21, and 167.86 ppm (Figure 1e), and
the spectrum of OPA3′ with three azomethines shows 12
peaks (Figure 1f). OPA2 and a model compound 3 had
simple spectra due to no E/ Z isomers (Figures 1a, d). In
the case of the cyclic compounds, the spectrum of CPA
that has three azomethines shows only one peak at-
tributed to the azomethine carbon, because CPA has only
one conformation with a symmetrical structure (Figure
1g).
zophenone (Run 2). The yield is considerably higher than
those of previously reported cyclizations, such as those
of carbonate and thiophenylene compounds.4 As a side-
product, poly(R-phenyl)phenylazomethine (PPA) was ob-
tained in this reaction. In the case of using TiCl4, the
high yield and the selectivity of the CPA were caused by
the bulky substituents at the R-position of the substrate.
The dehydration of 4-amino-4′-octylaminobenzophenone
resulted in the formation of the corresponding cyclic
trimer (CPA-b) in a 49% yield (Run 3). The dehydration
of 4-amino-4′-dioctylaminobenzophenone gave the corre-
sponding trimer (CPA-c) with a 92% isolated yield (Run
4).9 On the other hand, a different reaction behavior was
observed in the presence of PTS. The dehydration of 4′-
aminoacetophenone by PTS gave the corresponding
polymer, similar to the dehydration by TiCl4 (Run 5),
but CPA-a was obtained with a 90% yield by the
dehydration of 4-aminobenzophenone (Run 6). Contrary
to the case of TiCl4, a bulky substituent produced a lower
UV-vis spectroscopy often provides useful information
about the conformation of molecules. The UV-vis spec-
trum of CPA-a shows the shortest λmax absorbed π-π*
transition of the azomethine moiety at 318 nm (Figure
2). For the OPAs, the absorption based on the π-π*
(9) FAB-MS spectra of CPAs show no contamination of the other
cyclic oligomers.

5682 J . Org. Chem., Vol. 65, No. 18, 2000
Higuchi et al.
F igu r e 3. The result of the MM2 calculation of CPA-a.
Sch em e 4. In tr a m olecu la r Deh yd r a tion of th e
Lin ea r Tr im er w ith Z,Z Con for m a tion
F igu r e 1. The 13C NMR spectra of a) OPA2, b) OPA3, c)
OPA4, d) a model compound 3, e) OPA2′, f) OPA3′, and g)
CPA-a in CF3COOD.
of CPA is also supported by the NMR data. These
results support the idea that CPA has only the Z
conformation.
Th er m osta bility of CP A-a , OP As, OP A’s, P P A. The
obtained phenylazomethine compounds have a high
thermostability due to the imine bond, which has a large
bond energy (615 kJ /mol). The temperatures for a 5%
weight loss (Td5%) of OPA2, 3, 4, 2′, 3′, and PPA were
determined to be 301, 368, 438, 326, 397, and 508,
respectively, based on the thermogravimetric analysis.
The Td5% increased with an increase in the degree of
polymerization and capping with aniline. CPA-a shows
a good Td5% at 404 °C, which was close to that of OPA3′,
due to no end group in the chain.
Th e Cou p lin g Mech a n ism . Dehydration agents dras-
tically influenced the synthesis of the CPAs (Scheme 2).
The CPAs are formed through the intramolecular cou-
pling of the linear trimer with the Z,Z conformation
(Scheme 4). Because the dehydration using TiCl4 is an
irreversible reaction, the formation of CPAs is simply
dominated by the conformation, that is, the formation
ratio of the E/ Z isomers. The Z isomer of OPA3 is formed
with about a 50% yield, which was confirmed by the NMR
spectrum.10 Therefore, CPA-a is theoretically formed in
25% (0.52) yield, which agrees with the experimental one
of 20%. The higher yields of CPA-b and -c are based on
the preferential formation of the Z isomer due to steric
effects of the bulky substituents. On the other hand, the
dehydration using PTS is an equilibrium reaction, in
which the ratio of the isomers is controlled by the
thermodynamic process. Therefore, the exchange reaction
F igu r e 2. The UV-vis spectra of a) OPA2, b) OPA3, c) OPA4,
and d) CPA-a.
transition of azomethine shifts to the longer wavelength
according to the conformation. The E and Z isomers
possess different electronic structures, of which the
absorption band of the E isomer is shifted by about
20-50 nm to a longer wavelength than that of the Z
isomer due to elongation of the π-conjugation. A MM2
calculation of CPA-a with only the Z conformation
indicated that the three phenyl rings in the cyclic trimer
do not have a coplanar structure (Figure 3). The structure
of the E isomer possesses a distortion that is too large,
as indicated by the large formation energy calculated
by molecular modeling. Besides, the single conformation
(10) No thermal isomerization of OPA3 was confirmed up to 130 °C
in the NMR measurement.

Novel Cyclic Phenylazomethine Trimers
J . Org. Chem., Vol. 65, No. 18, 2000 5683
Sch em e 5. Exch a n ge betw een th e E a n d Z
Exp er im en ta l Section
Isom er s via Tr a n sa m in a tion
Syn t h esis of CP A-a u sin g TiCl4 a s a Deh yd r a t ion
Agen t. To a mixture of 4-aminobenzophenone (4.93 g, 25.0
mmol) and 1,4-diazabicyclo[2,2,2]-octane (DABCO) (8.41 g, 75.0
mmol) in chlorobenzene (150 mL) was added TiCl4 (3.56 g, 18.8
mmol), dropwise. The addition funnel was rinsed with chlo-
robenzene (5 mL). The reaction mixture was heated in an oil
bath at 125 °C for 15 h. The precipitate, including CPA-a, was
isolated by filtration. To R-chloronaphthalene (200 mL) was
added the filter cake; the heterogeneous solution was stirred
at 190 °C for 3 h. The R-chloronaphthalene solution was
separated by hot filtration. CPA-a (0.890 g, 4.96 mmol, 20%
yield) was isolated by precipitation from methanol.
Syn t h esis of CP A-a u sin g P TS a s
a Deh yd r a t ion
Agen t. A mixture of 4-aminobenzophenone (5.92 g, 30.0 mmol)
and PTS monohydrate (286 mg, 1.50 mmol) in p-xylene (300
mL) was refluxed with stirring for 16 h. The condenser was
fitted with a Dean-Stark water trap. After the mixture was
cooled and concentrated, CPA-a (4.82 g, 8.96 mmol, 90%) was
isolated by precipitation with methanol.
Syn t h esis of CP A-b u sin g TiCl4 a s a Deh yd r a t ion
Agen t. To a mixture of 4-amino-4′-octylaminobenzophenone
(0.195 g, 0.60 mmol) and DABCO (0.202 g, 1.80 mmol) in
chlorobenzene (6 mL) was added TiCl4 (0.085 g, 0.45 mmol),
dropwise. The addition funnel was rinsed with chlorobenzene
(1 mL). The reaction mixture was heated in an oil bath at 125
°C for 15 h. The precipitate was removed by filtration. The
filtrate was concentrated, and CPA-b (0.090 g, 49%) was
isolated by silica gel column chromatography (ethyl acetate:
hexane ) 1:10, including 2% Et3N, Rf ) 0.1).
Syn t h esis of CP A-b u sin g P TS a s
a Deh yd r a t ion
Agen t. A mixture of 4-amino-4′-octylaminobenzophenone (0.649
g, 2.00 mmol) and PTS monohydrate (19.1 mg, 0.100 mmol)
in p-xylene (20 mL) was refluxed with stirring for 16 h. The
condenser was fitted with a Dean-Stark water trap. After the
mixture was cooled and concentrated, CPA-b (0.194 g, 0.211
mmol, 32%) was isolated by silica gel column chromatography
(ethyl acetate/hexane ) 1:10, including 2% Et3N, Rf ) 0.1).
Syn th esis of CP A-c. To a mixture of 4-amino-4′-diocty-
laminobenzophenone (0.10 g, 0.23 mmol) and DABCO (0.077
g, 0.69 mmol) in chlorobenzene (5 mL) was added TiCl4 (0.033
g, 0.17 mmol), dropwise. The additional funnel was rinsed with
chlorobenzene (1 mL). The reaction mixture was heated in an
oil bath at 125 °C for 15 h. The precipitate was removed by
filtration. The filtrate was concentrated, CPA-c (0.089 g, 92%)
was isolated by silica gel column chromatography (ethyl
acetate/hexane ) 1:10, including 2% Et3N, Rf ) 0.2).
Syn th esis of Lin ea r Oligop h en yla zom eth in es (OP As).
To a mixture of 4-aminobenzophenone (0.986 g, 5.00 mmol),
benzophenone (4.56 g, 25.0 mmol), and DABCO (1.68 g, 15.0
mmol) in chlorobenzene (40 mL) was added TiCl4 (0.711 g, 3.75
mmol), dropwise. The addition funnel was rinsed with chlo-
robenzene (5 mL). The reaction mixture was heated in an oil
bath at 125 °C for 15 h. The precipitate was removed by
filtration. The filtrate was concentrated, OPA2 (0.946 g, 52%),
OPA3 (0.713 g, 29%), and OPA4 (0.121 g, 10%) were isolated
by silica gel column chromatography (ethyl acetate/hexane )
1:10, including 2% Et3N, Rf ) 0.2, 0.15, and 0.1, respectively).
Syn th esis of a Mod el Com p ou n d 3. To a mixture of
aniline (511 mg, 5.49 mmol), benzophenone (984 mg, 5.40
mmol), and DABCO (1.85 g, 16.5 mmol) in chlorobenzene (50
mL) was added TiCl4 (782 mg, 4.12 mmol), dropwise. The
addition funnel was rinsed with chlorobenzene (2 mL). The
reaction mixture was heated in an oil bath at 125 °C for 2 h.
The precipitate was removed by filtration. The filtrate was
concentrated, and 3 (1.27 g, 4.93 mmol, 91%) was isolated by
silica gel column chromatography (ethyl acetate/hexane ) 1:5,
Rf ) 0.6).
between the E/ Z isomers occurs through the transami-
nation (Scheme 5). In addition, the resulting CPA-a is
insoluble in the reaction solvent, so the formation of
CPA-a has a possibility to be accelerated in the equilib-
rium reaction. However, PTS was not useful for the
dehydration of the monomers substituted with alkylami-
nophenyl groups at the R-position because the π-conjuga-
tion of the monomers to the aminophenyl group at the
R-position lowers the electrophilicity of the carbonyl
carbon.
Con clu sion
Novel cyclic phenylazomethine trimers were synthe-
sized with high yields via the dehydration of the 4-ami-
nobenzophenone derivatives in the presence of TiCl4 or
PTS. In the case using TiCl4 as a dehydration agent, the
introduction of bulky substituents at the R-position of the
substrate enhanced the yields of the cyclic trimers. On
the other hand, PTS was specifically useful in the
synthesis of the phenyl-substituted cyclic trimer. This
different reactivity between TiCl4 and PTS depends on
each dehydration mechanism. The cyclic trimers were
confirmed by NMR, UV-vis spectra, and the result of
the MM2 calculation to have only the Z conformation and
a nonconjugated structure compared to the linear oli-
gophenylazomethines. This method is expected to provide
an efficient synthesis of the cyclic trimers as a monomer
of the polyphenylazomethine with high molecular weight
and high thermostability.
Syn th esis of An ilin e-Ca p p ed OP As (OP A’s). To a mix-
ture of 4-aminobenzophenone (3.94 g, 20.0 mmol), benzophe-
none (7.29 g, 40.0 mmol), and DABCO (20.19 g, 180.0 mmol)
in chlorobenzene (200 mL) was added TiCl4 (2.85 g, 15.0 mmol),
dropwise. The addition funnel was rinsed with chlorobenzene
(5 mL). The reaction mixture was heated in an oil bath at 125

5684 J . Org. Chem., Vol. 65, No. 18, 2000
Higuchi et al.
°C for 3 h. After the reaction mixture cooled, aniline (4.66 g,
50.0 mmol) and TiCl4 (5.70 g, 30.0 mmol) were added. The
reaction mixture was further heated in an oil bath at 125 °C
for 4 h. The precipitate was removed by filtration. The filtrate
was concentrated; OPA2′ (2.06 g, 4.71 mmol, 24%) and OPA3′
(1.33 g, 2.16 mmol, 22%) were isolated by silica gel column
chromatography (ethyl acetate/hexane ) 1:5, including 1.5%
Et3N, Rf ) 0.5 and 0.45, respectively).
11167273) and for Scientific Research from the Ministry
of Education Science Foundation Culture (No 11555253)
and Kanagawa Academy Science and Technology Re-
search Grant, and Kawakami foundation.
Su p p or tin g In for m a tion Ava ila ble: All characterization
data (1H-, 13C NMR, IR, MS, elemental analysis) of CPAs,
OPAs, a model compound 3, and OPA’s. This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was partially sup-
ported by a Grant-in-Aid for priority area (Nos 11136245,
J O000509C