Thermal decomposition of N-alkylated-2-amino-benzophenones

Article abstract of DOI:10.3987/COM-08-11626

Thermal decomposition of N-alkylated 2-aminobenzophenones 1a-d was studied at 400-560 °C, using calcium oxide as catalyst. The reactions yielded both 5- and 6-membered heterocyclic compounds. The N-methylated-2-aminobenzophenones 1a-b decomposed at 400-56

Full text of DOI:10.3987/COM-08-11626

HETEROCYCLES, Vol. 78, No. 6, 2009
1549
HETEROCYCLES, Vol. 78, No. 6, 2009, pp. 1549 - 1556. © The Japan Institute of Heterocyclic Chemistry
Received, 15th December, 2008, Accepted, 4th February, 2009, Published online, 6th February, 2009
DOI: 10.3987/COM-08-11626
THERMAL
DECOMPOSITION
OF
N-ALKYLATED-2-AMINO-
BENZOPHENONES
Evelyn Cuevas Creencia,a* Atsushi Takahashi,b and Takaaki Horaguchib*
aDepartment of Chemistry, College of Science and Mathematics, MSU-Iligan
Institute of Technology, Iligan City 9200, Philippines, email:
b
ec.creencia@gmail.com; Department of Chemistry, Faculty of Science, Niigata
University,
Ikarashi,
Niigata
950-2181,
Japan,
email:
hora@chem.sc.niigata-u.ac.jp
Abstract – Thermal decomposition of N-alkylated 2-aminobenzophenones 1a-d
was studied at 400-560 oC, using calcium oxide as catalyst. The reactions yielded
both
5-
and
6-membered
heterocyclic
compounds.
The
o
N-methylated-2-aminobenzophenones 1a-b decomposed at 400-560 C to give
2-phenylindole 2 (47% at 500 oC from 1b), acridine 4 and phenanthridine 5, while
the N-benzylated-2-aminobenzophenones 1c-d decomposed at 400-560 oC to give
o
o
2,3-diphenylindole 3 (33% at 450 C and 400 C from 1c and 1d, respectively),
acridine 4 and phenanthridine 5.
Thermal decomposition reaction is an interesting reaction to investigate since it can give a variety of
products – some expected while others are unexpected, interesting, and useful in other fields of science.1
The formation of the different products may even occur via different reaction mechanisms. Several
literatures report on the synthesis of carbazole by heating 2-nitrobiphenyl with deoxygenating agent such as
iron(II) oxalate2 or triethyl phosphite3. Krbechek and Takimoto reported that thermal decomposition of
o-substituted phenylazides, whenever possible, generally leads to 5-membered-ring structures.4 The
formation of the cyclic products from the nitro- or azido-compounds were found to occur via the nitrene
intermediate.5 Primary arylamines were also found to undergo dehydrocyclization reactions at 400-700 oC
to yield carbazoles and phenoxazine, as reported by Horaguchi, et al.6 On the other hand, Tsang, et al
reported the formation of N-substituted carbazoles from substituted arylamines by heating at 120 oC in the
presence of either palladium or copper catalyst.7
In our laboratory, we have studied thermal decomposition of a number of aromatic amines by subjecting
them to high temperatures using specialized apparatus in the presence of calcium oxide catalyst (Scheme 1).

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HETEROCYCLES, Vol. 78, No. 6, 2009
Thermal decomposition of 2-aminobiphenyl yielded carbazole (80% at 560 oC)8 while the
N-alkylated-2-aminobiphenyls gave several products: carbazole, methyl carbazole, phenanthridine and
phenanthrene.9 Thermal decomposition of N-alkyl-2-benzylanilines yielded acridine, anthracene,
2-phenylindole
and
2,3-diphenylindole
while
thermal
decomposition
of
N-alkyl-N’-phenyl-o-phenylenediamines yielded acridine, phenazine and 2-phenylbenzimidazole.10 We
have proposed the formation of all these products to occur via nucleophilic substitution on the aromatic ring,
a rather rare reaction mechanism, except for the phenylindoles and the benzimidazole which were formed
by the reaction of either a carbanion or amide ion with an imine carbon.
In this paper, we report the results of thermal decomposition of N-alkylated-2-aminobenzophenones and
compared these with our previous studies.
H
8)
NH2
N
CaO
Me
H
N
N
NR1R2
9)
N
CaO
+
+
+
R1 = H, R2 = Me
R1 = Me, R2 = Me
NR1R2
H
H
N
10)
N
N
CaO
+
+
+
R1 = H, R2 = Me
R1 = Me, R2 = Me
R1 = H, R2 = CH2Ph
R1 = CH2Ph, R2 = CH2Ph
NR1R2
H
10)
N
N
CaO
N
+
+
N
N
H
R1 = Me, R2 = Me
R1 = CH2Ph, R2 = Ch2Ph
Scheme 1. Thermal decomposition reactions of aromatic amines
The starting materials used were prepared either by methylating or benzylating 2-aminobenzophenone as
o
described in the Experimental Section. When heated at 400-560 C in the presence of calcium oxide
catalyst, 2-methylaminobenzophenone 1a yielded 2-phenylindole 2 (15-32%) with highest yield obtained
o
at 400 C (32%), acridine 4 (3-17%) and phenanthridine 5 (3-10%) (Table 1, Entries 1-4). With
o
2-dimethylaminobenzophenone 1b, the products formed by thermal decomposition at 400-500 C were
o
2-phenylindole 2 (38-47%) with highest yield obtained at 500 C (47%), acridine 4 (4-6%) and
o
phenanthridine 5 (11-21%) (Table 1, Entries 5-7). While thermal decomposition at 450-600 C of

HETEROCYCLES, Vol. 78, No. 6, 2009
1551
2-aminobenzophenone8 yielded acridine (3-7%), acridone (21-32%) and carbazole (2-14%), the
N-methylated-2-aminobenzophenone produced other products, 2-phenylindole 2 and phenanthridine 5,
aside from acridine 4 (Scheme 2).
No carbazole and acridone were detected from the thermal decomposition of 2-methylamino-
benzophenone 1a and 2-dimethylaminobenzophenone 1b. When 2-benzylaminobenzophenone 1c was
o
heated at 400-500 C in the presence of calcium oxide catalyst, 2,3-diphenylindole 3 (28-33%) with
R2
NCH2R1
H
N
N
CaO
N
+
R1
H
R2
H
Ph +
O
1a
1b
5
2
4
1a, 1b
H
Me
R2
1c
1d
Ph
Ph
H
NCH2R1
H
CH2Ph
N
N
CaO
N
+
Ph +
Ph
O
1c, 1d
5
3
4
Scheme 2. Thermal decomposition reactions of N-alkylated-2-aminobenzophenones 1a-d
Thermal decompositiona of 2-methylaminobenzophenone 1a and 2-dimethylamino-
Table 1.
benzophenone 1b
Starting
Reaction
temperature
(oC)
Reaction
timec
(minutes)
Conversion
(%)
Product Yieldd %
Entry
materialb
2
4
14
17
14
3
5
6
1
2
3
4
5
6
7
1a
1a
1a
1a
1b
1b
1b
400
450
500
560
400
450
500
40
40
40
40
40
40
40
100
100
100
100
100
100
100
32
23
22
15
46
38
47
9
10
3
5
11
16
21
6
4
a: Nitrogen carrier gas at 19mL/minute; b: 1.0 mmol; c: The reaction time corresponds to the time in minutes for the
traveling furnace to reach the stationary furnace. (see Experimental section); d: Based on reacted starting material.

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HETEROCYCLES, Vol. 78, No. 6, 2009
o
highest yield obtained at 450 C (33%), acridine 4 (3-5%) and phenanthridine 5 (7-11%) were produced
(Table 2, Entries 1-3). 2-Dibenzylaminobenzophenone 1d also yielded 2,3-diphenylindole 3 (17-33%)
Table 2.
benzophenone 1d
Thermal decompositiona of 2-benzylaminobenzophenone 1c and 2-dibenzylamino-
Starting
Reaction
temperature
(oC)
Reaction timec Conversion
Product Yieldd (%)
Entry
materialb
(minutes)
(%)
3
4
5
5
1
2
3
4
5
6
7
1c
1c
1c
1d
1d
1d
1d
400
450
500
400
450
500
560
40
40
40
40
40
40
40
100
100
100
100
100
100
100
28
33
30
33
30
24
17
11
10
7
4
3
14
16
10
8
6
4
4
5
a: Nitrogen carrier gas at 19mL/minute; b: 1.0 mmol; c: The reaction time corresponds to the time in minutes for the
traveling furnace to reach the stationary furnace. (see Experimental section); d: Based on reacted starting material.
H
-H2O
H
N
(1a)
R1H2C
R1HC
R2
R2
N
N R2
H
N
+H+
-H+
N
O
R1
H
rearrangement
cyclization
HO
H
O
2
1a-d
H
N
-H2O
H
+
-R2
+H+
R1 R2
(1b)
1a
1b
H
H
H
Me
H
1c Ph
1d Ph CH2Ph
-H2O
(1c)
H
N
-H2O
3
+
-R2
+H+
(1d)
Scheme 3. Proposed mechanism for the formation of 2-phenylindole and 2,3-diphenylindole from thermal
decomposition of N-alkylated-2-aminobenzophenones (1a-d)

HETEROCYCLES, Vol. 78, No. 6, 2009
1553
o
with highest yield obtained at 400 C (33%), acridine 4 (8-16%) and phenanthridine 5 (4-6%) (Table 2,
o
Entries 4-7), when heated at 400-560 C in the presence of calcium oxide catalyst (Scheme 2). Again,
no acridone and carbazole were detected but instead another product, 2,3-diphenylindole 3, was identified.
The formation of 2-phenylindole 2 and 2,3-diphenylindole 3 could have occurred by the abstraction of H+
from the methyl or benzyl substituent by the calcium oxide catalyst followed by cyclization and
rearrangement to give the final product (Scheme 3). It is interesting to note that the presence of methyl
and benzyl groups on the nitrogen of 2-aminobenzophenone changed its chemistry and afforded other
products, not observed with the unsubstituted aromatic amine, during thermal decomposition. Hence, a
variety of other products may be obtained from thermal decomposition reactions by introducing other
substituents on the aromatic amine substrates.
EXPERIMENTAL
Melting points are uncorrected. Column chromatography was performed on silica gel (Wakogel C-200).
Unless otherwise stated, anhydrous sodium sulfate was employed as the drying agent. The IR spectra
were determined on a Hitachi model 270-30 IR Spectrophotometer. The 1H and 13C NMR spectra were
determined at 500MHz and 125MHz, respectively, on a Varian Unity plus-500W NMR
Spectrophotometer, using tetramethylsilane as the internal standard.
General Procedure for the Thermolysis Reaction10 of N-Alkylated-2-aminobenzophenones.
Elemental analysis apparatus (Micro Elemental Analyzer, Mitamura Riken Kogyo Inc.) was used for the
thermolysis reaction. Granules of calcium oxide were obtained by grinding large pieces of calcium
oxide (Nakalai Tesque, Inc.) and collecting particles which passed through the 5 mm sieve and retained
by the 2 mm sieve. A quartz tube (66 cm in length, 12 mm i.d.) was packed to a length of 28 cm with
the calcium oxide granules (18.0 g). The tube was positioned in the horizontal stationary furnace with
heating coils (38 cm in length). The tube was then purged with N2 gas at a rate of about 19 mL/min and
kept at this condition throughout the experiment. The stationary furnace was heated to the desired
o
reaction temperature (400-560 C). Starting material (1.0 mmole) was weighed into a quartz boat and
placed inside the reaction tube at 3 cm from the stationary furnace and vaporized by the traveling furnace
o
o
o
under N2 gas environment. When the desired reaction temperature was 400 C, 450 C or 500 C, the
stationary furnace was heated to 400 oC, 450 oC or 500 oC while the traveling furnace was heated to 560
oC. When the desired reaction temperature was 560 oC, the stationary furnace was heated to the desired
o
temperature while the traveling furnace was heated 50 C higher than the reaction temperature. The
traveling furnace was set to motion gradually, reached the stationary furnace in 35 minutes and kept for 5
minutes at this state. Products which came out from the outlet (5 mm i.d.) of the quartz tube were
collected in a vessel cooled with ice-water. The products were extracted with acetone. After removal of

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HETEROCYCLES, Vol. 78, No. 6, 2009
the acetone, the residue was chromatographed on a silica gel column and eluted with benzene,
benzene-hexane or hexane-EtOAc to give various products. Structures of the products were determined
from their spectra. 2-Phenylindole 2, acridine 4, and phenanthridine 5 were identified by comparison of
1
the IR, H NMR and 13C NMR spectra with those of commercially available samples while
2,3-diphenylindole 3 was identified by comparison of its spectral data with literature value.
Synthesis of 2-methylaminobenzophenone 1a and 2-dimethylaminobenzophenone 1b.
2-Aminobenzophenone (1.978 g, 10.03 mmol) was placed in a 50 mL round bottom flask and added with
dimethyl sulfoxide (4mL), tripotassium phosphate (1.589 g, 7.49 mmol), and methyl iodide (1.0 mL,
16.06 mmol). The mixture was heated in an oil bath at 50 oC for 2 h. The progress of the reaction was
monitored by thin layer chromatography. After 2 h, methyl iodide (0.8 mL, 12.85 mmol) was again
o
added and the mixture heated for another 1 h in the oil bath at 50 C. The mixture was then extracted
with EtOAc, washed with water and the organic layer separated and dried over anhydrous sodium sulfate.
The filtrate was concentrated in a rotary evaporator. The resulting solution was chromatographed on a
silica gel column using hexane:EtOAc (15:1) as eluting solvent.
The reaction yielded
2-methylaminobenzophenone 1a (0.769 g, 36%), yellow crystals recrystallized in EtOH, and
2-dimethylaminobenzophenone 1b (0.790 g, 35%), yellow liquid.
o
o
2-Methylaminobenzophenone (1a).11 mp (EtOH) 66-67 C (lit.,11 mp 65-69 C); IR (KBr) 3340 cm-1
1
(NH), 1616 cm-1 (CO); H NMR (CDCl3): δ 2.97 (d, J=5.0 Hz, 3H, CH3), 6.54 (dd, J=8.0 Hz and 8.0
Hz, 1H, Ar-H), 6.76 (d, J=8.5 Hz, 1H, Ar-H), 7.40-7.52 (m, 5H, 5 Ar-H), 7.59 (d, J=8.0 Hz, 2H, 2 Ar-H),
8.54 (broad s, 1H, N-H ); 13C NMR: (CDCl3): δ 29.4 (q), 111.1 (d), 113.6 (d), 117.2 (s), 128.0 (d),
128.9 (d), 130.6 (d), 135.0 (d), 135.5 (d), 140.6 (s), 152. 7 (s), 199.3 (s).
2-Dimethylaminobenzophenone (1b). IR (film): 1652 cm-1 (CO); 1H NMR (CDCl3): δ 2.70 (s, 6H, 2
CH3), 6.90 (dd, J=8.0 Hz and 8.0 Hz, 1H, Ar-H), 6.99 (d, J=8.0 Hz, 1H, Ar-H), 7.32 (d, J=8.0 Hz, 1H,
13
Ar-H), 7.38 – 7.43 (m, 3H, 3 Ar-H), 7.54 (t, J=8.5 Hz, 1H, Ar-H), 7.83 (d, J=8.5 Hz, 2H, 2 Ar-H); C
NMR (CDCl3): 43.4 (q), 116.4 (d), 118.8 (d), 128.0 (s), 128.1 (d), 129.9 (d), 130.7 (d), 131.4 (d), 132.6
(d), 137.7 (s), 151.6 (s), 198.2 (s).
Synthesis of 2-benzylaminobenzophenone 1c and 2-dibenzylaminobenzophenone 1d.
2-Aminobenzophenone (1.975 g, 10.01 mmol) was placed in a 50 mL round bottom flask containing
dimethyl sulfoxide (4 mL). Tripotassium phosphate (1.601 g, 7.54 mmol) and benzyl bromide (1.5 mL,
12.64 mmol) was then added and the mixture was heated in an oil bath at 50 oC for 3 h. The progress of
the reaction was monitored by thin layer chromatography. After 3 h, benzyl bromide was added (1.0 mL,
8.42 mmol) and heating was continued for another 2 h. The resulting solution was extracted with

HETEROCYCLES, Vol. 78, No. 6, 2009
1555
EtOAc, washed with water and the organic layer was separated. The organic layer was dried with
anhydrous sodium sulfate. The filtrate was then concentrated in a rotary evaporator. The resulting
solution was chromatographed on a silica gel column using benzene:hexane (3:1) as the eluting solvent.
The reaction yielded 2-benzylaminobenzophenone 1c (1.208 g, 42%), yellow crystals recrystallized in
hexane, and 2-dibenzylaminobenzophenone 1d (1.171 g, 31%), yellow liquid.
2-Benzylaminobenzophenone (1c).12 mp (hexane): 81-82 oC (lit.,12 mp 84-86 oC), IR (KBr): 3340 cm-1
(NH), 1628 cm-1 (CO); 1H NMR (CDCl3): δ 4.49 (d, J=6.0 Hz, 2H, CH2), 6.63 (d, J=9.0 Hz, 1H, Ar-H),
7.26 – 7.39 (m, 7H, 7 Ar-H), 7.46 – 7.64 (m, 6H, 6 Ar-H), 8.94 (broad s, 1H, N-H); 13C NMR (CDCl3): δ
46.9 (t), 105.5 (s), 114.0 (d), 118.8 (d), 127.0 (d), 127.3 (d), 128.2 (d), 128.7 (d), 129.0 (d), 131.3 (d),
136.9 (d), 137.4 (d), 137.9 (s), 139.6 (s), 150.3 (s), 198.2 (s).
1
2-Dibenzylaminobenzophenone (1d). IR (film): 1658 cm-1 (CO); H NMR (CDCl3): δ 4.01 (s, 4H, 2
CH2), 6.79 – 6.85 (m, 4H, 4 Ar-H), 6.98 (d, J=8.0 Hz, 1H, Ar-H), 7.08 – 7.18 (m, 7H, 7 Ar-H), 7.34 –
7.39 (m, 2H, 2 Ar-H), 7.44 – 7.47 (m, 2H, 2 Ar-H), 7.59 – 7.63 (m, 1H Ar-H), 7.76 (d, J=8.0 Hz, 2H, 2
13
Ar-H); C NMR (CDCl3): δ 56.5 (t), 121.6 (s), 122.0 (d), 127.0 (d), 128.0 (d), 128.4 (d), 128.7 (d),
129.5 (d), 129.7 (d), 130.7 (d), 132.8 (d), 134.4 (d), 137.1 (s), 138.3 (s), 149.9 (s), 199.1 (s).
o
1
2-Phenylindole (2). mp (EtOH) 187-188 C; IR (KBr): 3444 cm-1 (NH); H NMR (CDCl3): δ 6.83 (s,
1H, indole C3-H), 7.12 (dd, J=8.0 Hz and 8.0 Hz, 1H, Ar-H), 7.20 (dd, J=8.0 Hz and 8.0 Hz, 1H, Ar-H),
7.32 (dd, J=8.0 Hz and 8.0 Hz, 1H, Ar-H), 7.40 (d, J=8.0 Hz, 1H, Ar-H), 7.45 (dd, J=8.0 Hz and 8.0 Hz,
2H, 2 Ar-H), 7.63 (d, J=8.0 Hz, 1H, Ar-H), 7.67 ( d, J=8.0 Hz, 2H, 2 Ar-H), 8.33 (broad s, 1H, NH); 13C
NMR (CDCl3): δ 100.0 (d), 110.9 (d), 120.2 (d), 120.6 (d), 122.3 (d), 125.1 (d), 127.7 (d), 129.0 (d),
129.2 (s), 132.3 (s), 136.8 (s), 137.9 (s).
o
1
2,3-Diphenylindole (3). mp (EtOH) 120-123 C (lit.,13 mp 122-124 oC); IR (KBr) 3400 cm-1 (NH); H
NMR (CDCl3): δ 7.15 (dd, J=7.5 Hz and 7.5 Hz, 1H, Ar-H), 7.25 (dd, J=7.5 Hz and 7.5 Hz, 1H, Ar-H),
7.29 (dd, J= 7.5 Hz and 7.5 Hz, 1H, Ar-H), 7.31 (dd, J=7.5 Hz and 7.5 Hz, 1H, Ar-H), 7.33 (dd, J=7.5 Hz
and 7.5 Hz, 2H, 2 Ar-H), 7.38 (dd, J=7.5 Hz and 7.5 Hz, 2H, 2 Ar-H), 7.42 – 7.46 (m, 5H, 5 Ar-H), 7.68
(d, J=7.5 Hz, 1H, Ar-H), 8.23 (s, 1H, NH); 13C NMR (CDCl3): δ 110.9 (d), 115.0 (s), 119.7 (d), 120.4 (d),
122.7 (d), 126.2 (d), 127.7 (d), 128.2 (s), 128.5 (d), 128.7 (d), 128.7 (d), 130.1 (d), 132.7 (s), 134.1 (s),
135.0 (s), 135.9 (s). Spectral properties are identical with those in the literature.14
ACKNOWLEDGEMENT
ECC would like to thank the Japan Society for the Promotion of Science (JSPS) for the research grant at
Niigata University, Japan.

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