Synthesis of benzimidazole-fused heterocycles by intramolecular oxidative C-N bond formation using hypervalent iodine reagents

Article abstract of DOI:10.1055/s-0030-1260192

A straightforward approach by dehydrogenative C-N coupling between aryl C-H and N-H bonds using a hypervalent iodine reagent under mild conditions offers a versatile and convenient method for synthesizing various benzimidazole-fused heterocycles. Georg Th

Full text of DOI:10.1055/s-0030-1260192

PAPER
3235
Synthesis of Benzimidazole-Fused Heterocycles by Intramolecular Oxidative
C–N Bond Formation Using Hypervalent Iodine Reagents
H
ypervalent Iodine
o
-Mediate
d
B
r
e
nzimid
i
azole-F
k
usedSynthe
i
sis Kutsumura,* Shinichi Kunimatsu, Kimiko Kagawa, Takashi Otani, Takao Saito*
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Fax +81(3)52614631; E-mail: nkutsu@rs.kagu.tus.ac.jp; E-mail: tsaito@rs.kagu.tus.ac.jp
Received 20 June 2011; revised 6 July 2011
bination of reagent PhI=NTs (1.1 equiv) and a catalytic
Abstract: A straightforward approach by dehydrogenative C–N
amount of Cu(OTf)2 (5 mol%) (Table 1, entry 6, 74%).3
Moreover, satisfactory results were obtained using two
coupling between aryl C–H and N–H bonds using a hypervalent io-
dine reagent under mild conditions offers a versatile and convenient
equivalents of reagent such as PhI(OCOCF3)2 (Table 1,
entry 3, 80%), and unsatisfactory results were obtained
using iodosobenzene and PhI(OAc)2 (Table 1, entries 1
and 2).
method for synthesizing various benzimidazole-fused heterocycles.
Key words: hypervalent iodine reagent, C–N bond forming cy-
clization, benzimidazole-fused heterocycles, straightforward syn-
thesis, mild conditions
Table 1 Screening of Hypervalent Iodine Reagents
S
For the synthesis of aza-heterocycles, oxidative intramo-
lecular C–N bond-forming cyclization is one of the most
straightforward methods. In the last decade,1 since
Breslow reported the first intramolecular catalytic nitrene
C–H insertion, one such type cyclization,1a hypervalent
iodine-mediated reaction, has attracted considerable at-
tention because of its low toxicity, high chemoselectivity,
and mild conditions. For example, Du Bois et al. pio-
neered intramolecular oxidative C–N bond formation to
afford oxazolidinones1b and cyclic sulfamates1c from a
combination of PhI(OAc)2, magnesium oxide, and a rhod-
ium(II) catalyst. Togo et al. reported the synthesis of 2,1-
benzothiazine derivatives from sulfonamides with
PhI(OH)OTs.1d Nishiyama et al. demonstrated the synthe-
sis of azaspiro- or quinolinone-type products from
PhI(OCH2CF3)2 generated electrochemically from iodo-
benzene.1e
S
N
NH
iodinane
N
N
1a
2a
Entry Reagent (equiv)
Conditions
Yield (%)
5
1
2
3
4
5
6
PhI=O (2)
CH2Cl2
r.t., 43 h
PhI(OAc)2 (2)
PhI(OCOCF3)2 (2)
PhI(OH)OTs (1.1)
PhI=NTs (1.1)
CH2Cl2
r.t., 45 h
51
80
82
0
A
B
CH2Cl2
0 °C to r.t., 43 h
MeCN
0 °C to r.t., 3 h
CH2Cl2
0 °C to r.t., 52 h
Benzimidazole-fused heterocycles have appealing biolog-
ical and pharmaceutical properties.2 To date, however,
very little is known about their systematic synthesis. We
describe herein the synthesis of various benzimidazole-
fused heterocycles from N-(1-azaheterocycle-2-yl)aniline
derivatives via oxidative intramolecular C–N bond forma-
tion using hypervalent iodine reagents.
PhI=NTs (1.1)
Cu(OTf)2 (5 mol%)
C
CH2Cl2
–40 to 0 °C, 5 h
74
To confirm the generality of this hypervalent iodine-me-
diated reaction, various N-dihydrothiazin-2-yl anilines 1
and N-dihydrothiazol-2-yl anilines 3 were examined un-
der three reagent conditions: using 2.0 equivalents of the
reagent PhI(OCOCF3)2 (reagent condition A), 1.1 equiva-
lents of the reagent PhI(OH)OTs (reagent condition B),
and 1.1 equivalents of the reagent PhI=NTs and a catalytic
amount of Cu(OTf)2 (reagent condition C) (Table 2).
Reactions of 1b having an o-toluidine group (R1 = Me;
R2 = R3 = H) by reagent conditions A, B, and C gave 3,4-
dihydro-9-methyl-2H-[1,3]thiazino[3,2-a]benzimidazole
(2b) in high yields (Table 2, entries 1–3). On the other
hand, cyclization reactions of 1c–e having a methyl, meth-
oxy, and fluoro group at the meta-position (R2 = Me,
OMe, F; R1 = R3 = H) gave 2 and/or 2¢ (Table 2, entries 4–
12). Moreover, reactions of 1f and 1g having a para sub-
Initially, we examined the efficiency of various hyperval-
ent iodine reagents for the synthesis of 3,4-dihydro-2H-
[1,3]thiazino[3,2-a]benzimidazole (2a) from 2-anilino-
4H-5,6-dihydro-1,3-thiazine (1a). For treatment of 1a
with a reagent (1.1 equiv) in acetonitrile from 0 °C to
room temperature for three hours to give 2a, best results
were obtained using the reagent PhI(OH)OTs (Table 1,
entry 4, 82%). On the other hand, use of PhI=NTs (1.1
equiv) gave no reaction (Table 1, entry 5). However, in-
triguingly, satisfactory results were obtained using a com-
SYNTHESIS 2011, No. 20, pp 3235–3240
x
x.
x
x
.
2
0
1
1
Advanced online publication: 24.08.2011
DOI: 10.1055/s-0030-1260192; Art ID: F62611SS
© Georg Thieme Verlag Stuttgart · New York

3236
N. Kutsumura et al.
PAPER
Table 2 Reaction of N-Dihydrothiazin-2-yl Anilines 1 and N-Dihydrothiazol-2-yl Anilines 3
S
S
n
S
n
n
N
NH
R1
N
N
A PhI(OCOCF3)2 (2.0 equiv), CH2Cl2, 0 °C to r.t.
B PhI(OH)OTs (1.1 equiv), MeCN, 0 °C to r.t.
C PhI=NTs (1.1 equiv), Cu(OTf)2 (5 mol%), CH2Cl2, –40 to 0 °C
iodinane
N
N
R1
R2
+
R2
R2
R3
R3
1 (n = 2)
3 (n = 1)
2 (n = 2)
4 (n = 1)
2' (n = 2)
Entry
Substrate
R1
R2
R3
Method
Time (h)
Yield (%)
2/4
2¢
1/3 (recovered)
1
2
1b
1b
1b
1c
1c
1c
1d
1d
1d
1e
1e
1e
1f
Me
Me
Me
H
H
H
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
6
1
79
91
81
26
24
38
32
23
18
21
trace
22
60
66
64
44
55
24
34
78
40
52
71
67
H
H
3
H
H
6
4
Me
Me
Me
H
29
4
21
20
38
29
19
47
5
H
H
6
H
H
4
7
H
OMe
OMe
OMe
F
H
21
10
9
8
H
H
9
H
H
16
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
H
H
26
20
20
67
5
13
17
61
H
F
H
trace
22
H
F
H
H
H
Me
Me
Me
OMe
OMe
OMe
H
1f
H
H
1f
H
H
3
1g
1g
1g
3a
3a
3a
3b
3b
3b
H
H
4
H
H
7
H
H
4
H
H
47
8
17
H
H
H
H
H
H
22
91
20
30
H
H
Me
Me
Me
H
H
H
H
stituent (R3 = Me, OMe; R1 = R2 = H) gave 2f and 2g in the reactions of 5a and 5b to give higher yields of 6a and
moderate yields (Table 2, entries 13–18). Similarly, reac- 6b, which were sensitive to acid (Table 3, entries 3, 4),4
tions of N-dihydrothiazol-2-yl anilines 3a and 3b gave the but did not affect the reactions of 5c (Table 3, entries 8–
corresponding 4a and 4b, respectively (Table 2, entries 10).
19–24).
The reactions of compounds 7 having a pyridine-modified
To extend the generality of this reaction, the syntheses of substituent were also examined (Table 4). Pyrido[1,2-
other benzimidazole-fused heterocycles were investigat- a]benzimidazole derivatives 8a,b and dipyrido[1,2-
ed. Hypervalent iodine-mediated reactions of N-oxazin-2- a:2¢,3¢-d]imidazole 8c were obtained in moderate yields
yl anilines 5 gave the corresponding benzimidazoles 6 (Table 4, entries 1–9).
(Table 3). The addition of 4 Å molecular sieves facilitated
Synthesis 2011, No. 20, 3235–3240 © Thieme Stuttgart · New York

PAPER
Hypervalent Iodine-Mediated Benzimidazole-Fused Synthesis
3237
In conclusion, we have achieved the synthesis of benzim-
idazole-fused heterocycles using hypervalent iodine re-
agents. The PhI(OH)OTs-mediated condition (reagent
condition B) tends to be efficient depending on the sub-
strate. We are extending this work by investigating hyper-
valent iodine-mediated oxidative intramolecular C–N
bond-forming cyclization.
Table 3 Reaction of N-Oxazin-2-yl Anilines 5
O
O
N
NH
N
iodinane
4 Å MS
N
a: R3 = H
R3
R3
b: R3 = Me
5
6
All melting points were determined on a Yanaco melting point ap-
paratus and are uncorrected. IR spectra were recorded on a Hitachi
Entry Substrate
Method Time (h) Yield (%)
1
270-30 or a Horiba FT-710 model spectrophotometer. H and 13C
1
2
3
4
5
6
7
5a
5a
5a
5a
5b
5b
5b
A
B
C
Cb
A
B
C
43
27
5
0a
76
NMR spectral data were recorded on a Bruker AV 600, a Jeol JNM-
EX 500, or a Jeol JNM-EX 300 instrument. Chemical shifts (d) are
1
quoted in ppm using TMS (d = 0 ppm) as internal standard for H
54
13
33
86
54
NMR spectroscopy, and CDCl3 (d = 77.0 ppm) for 13C NMR spec-
troscopy. Mass spectra were measured on a Bruker Daltonics mi-
croTOF or a Hitachi double-focusing M-80B spectrometer.
Elemental analyses were performed with a Yanaco CHN-Coder
MT-6 model analyzer. Column chromatography was conducted on
silica gel (Kanto Chemical Co. or Merck Co. Ltd). All reactions
were performed under an argon atmosphere.
17
32
3
9
The starting materials 1, 3, and 5 were prepared from the corre-
sponding amino alcohol derivatives and isothiocyanates by Loev’s
protocol5a or Heinelt’s protocol.5b Preparation and/or analytical data
for known compounds have been reported.6
O
N
Ab
Bb
Cb
25
3
7
34c
79
46
NH
8
9
10
Compounds 1 and 3; 2-Anilino-4H-5,6-dihydro-1,3-thiazine
(1a);5a Typical Procedure
5c
A mixture of 3-aminopropan-1-ol (0.61 mL, 8.0 mmol) and phenyl
isothiocyanate (1.0 mL, 8.4 mmol) in THF (20 mL) was stirred at
r.t. for 2 h. After evaporation, the residual crystals were collected by
suction filtration. The thiourea derivative was dissolved in concd
HCl (3.0 mL) and then heated at 80 °C for 3 h. After cooling to r.t.,
the mixture was made alkaline by the addition of aq 2.5 M NaOH
(15 mL) and then filtered by suction to afford 1a (1.3 g, 82% over 2
steps).
a Substrate 5a was recovered (91%).
b Without 4 Å molecular sieves.
c Substrate 5c was recovered (40%).
Table 4 Reaction of Pyridine-Modified Compounds 7
NH
N
1,3-Oxazin-2-amines 5; N-(p-Tolyl)-5,6-dihydro-4H-1,3-oxazin-
2-amine (5b);5b Typical Procedure
iodinane
N
X
N
X
A mixture of 3-aminopropan-1-ol (0.61 mL, 8.0 mmol) and 4-meth-
ylphenyl isothiocyanate (1.3 g, 8.4 mmol) in THF (20 mL) was
stirred at r.t. for 2 h. After evaporation, the residual crystals were
collected by suction filtration. The thiourea derivative was dis-
solved in THF (20 mL) and an aqueous solution of NaOH (0.80 g,
20.0 mmol) in H2O (10 mL) was added with stirring at r.t. Then a
solution of TsCl (1.9 g, 10.0 mmol) in THF (20 mL) was slowly
added and the mixture was stirred at the same temperature for 3 h.
After completion of the reaction, the solvent was evaporated and the
mixture was extracted with EtOAc (3 × 20 mL). The combined ex-
tracts were washed with brine (20 mL), dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by silica gel column
chromatography (EtOAc–Et3N, 100:1) to afford 5b (0.80 g, 53%
over 2 steps); colorless crystals; mp 117–118 °C.
a: X = CH, R3 = H
b: X = CH, R3 = Me
c: X = N, R3 = H
R3
7
R3
8
Entry
Substrate
7a
Method
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
A
B
C
A
B
C
A
B
C
6
2
33
52
30
62
73
44
65
74
44
7a
7a
6
7b
4
7b
2
IR (KBr): 1672, 1604, 1510, 1253 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.81–1.91 (m, 2 H), 2.25 (s, 3 H),
3.34 (dd, J = 6.1, 6.1 Hz, 2 H), 4.17 (dd, J = 5.4, 5.4 Hz, 2 H), 6.96–
7.05 (m, 4 H), 7.12 (br s, 1 H).
7b
4
7c
28
4
13C NMR (75 MHz, CDCl3): d = 20.4, 21.8, 40.1, 65.7, 120.8 (2 ×),
7c
128.9 (2 ×), 130.7, 140.0, 150.2.
7c
24
HRMS-EI: m/z [M]+ calcd for C11H14N2O: 190.1106; found:
190.1103.
Synthesis 2011, No. 20, 3235–3240 © Thieme Stuttgart · New York

3238
N. Kutsumura et al.
PAPER
Reagent Condition A; 3,4-Dihydro-2H-[1,3]thiazino[3,2-a]benz-
imidazole (2a);7 Typical Procedure (Table 1, Entry 3)
HRMS-EI: m/z [M]+ calcd for C11H12N2S: 204.0721; found:
204.0718.
To a solution of 1a (58 mg, 0.30 mmol) in CH2Cl2 (10 mL) was add-
ed PhI(OCOCF3)2 (260 mg, 0.60 mmol) at 0 °C. The reaction mix-
ture was stirred for 1 h, then the temperature was raised slowly to
r.t. After stirring for 42 h, the reaction was quenched with sat. aq
NaHCO3 (20 mL), and the mixture was extracted with CH2Cl2 (3 ×
10 mL). The combined extracts were washed with brine (10 mL),
dried (Na2SO4), and concentrated in vacuo. The residue was puri-
fied by silica gel column chromatography (EtOAc–Et3N, 100:1) to
afford 2a (46 mg, 80%).
3,4-Dihydro-6-methyl-2H-[1,3]thiazino[3,2-a]benzimidazole
(2¢c)
Colorless crystals; mp 129–130 °C.
IR (KBr): 1591, 1433, 1396, 1271 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.38–2.43 (m, 2 H), 2.63 (s, 3 H),
3.12 (dd, J = 5.6, 5.6 Hz, 2 H), 4.48 (dd, J = 5.9, 5.9 Hz, 2 H), 6.84
(d, J = 7.4 Hz, 1 H), 7.04–7.06 (m, 1 H), 7.42 (d, J = 7.9 Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 18.8, 21.5, 25.7, 45.1, 107.1,
115.9, 119.9, 124.0, 134.2, 142.9, 146.5.
HRMS-EI: m/z [M]+ calcd for C11H12N2S: 204.0721; found:
204.0723.
Reagent Condition B; 3,4-Dihydro-2H-[1,3]thiazino[3,2-a]benz-
imidazole (2a);7 Typical Procedure; (Table 1, Entry 4)
To a solution of 1a (58 mg, 0.30 mmol) in MeCN (10 mL) was add-
ed PhI(OH)OTs (130 mg, 0.33 mmol) at 0 °C. The reaction mixture
was stirred for 1 h, then the temperature was raised slowly to r.t. Af-
ter stirring for 2 h, the reaction was quenched with sat. aq NaHCO3
(20 mL), and the mixture was extracted with CH2Cl2 (3 × 10 mL).
The combined extracts were washed with brine (10 mL), dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
silica gel column chromatography (EtOAc–Et3N, 100:1) to afford
2a (47 mg, 82%).
3,4-Dihydro-8-methoxy-2H-[1,3]thiazino[3,2-a]benzimidazole
(2d)
Colorless crystals; mp 180–181 °C.
IR (KBr): 1616, 1589, 1425, 1151 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.42–2.49 (m, 2 H), 3.21 (t,
J = 5.7 Hz, 2 H), 3.84 (s, 3 H), 4.14 (dd, J = 6.1, 6.0 Hz, 2 H), 6.81
(dd, J = 8.8, 2.4 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 1 H), 7.12 (d, J = 2.4
Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 23.4, 25.7, 42.5, 55.9, 101.2,
107.9, 110.6, 130.3, 143.7, 146.7, 156.3.
Reagent Condition C; 3,4-Dihydro-2H-[1,3]thiazino[3,2-a]benz-
imidazole (2a);7 Typical Procedure (Table 1, Entry 6)
To a solution of 1a (58 mg, 0.30 mmol) in CH2Cl2 (10 mL) were
added PhI=NTs (120 mg, 0.33 mmol) and a catalytic amount of
Cu(OTf)2 (5.4 mg, 0.015 mmol) at –40 °C. The reaction mixture
was stirred at 0 °C for 5 h. The reaction was quenched with sat. aq
NaHCO3 (20 mL), and the mixture was extracted with CH2Cl2 (3 ×
10 mL). The combined organic extracts were washed with brine (10
mL), dried (Na2SO4), and concentrated in vacuo. The residue was
purified by silica gel column chromatography (EtOAc–
Et3N, 100:1) to afford 2a (42 mg, 74%).
1H NMR (300 MHz, CDCl3): d = 2.38–2.50 (m, 2 H), 3.19 (dd,
J = 5.7, 5.6 Hz, 2 H), 4.14 (dd, J = 6.1, 6.0 Hz, 2 H), 7.16–7.26 (m,
3 H), 7.61 (d, J = 7.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 23.3, 25.7, 42.1, 107.6, 119.9,
121.3, 122.3, 135.5, 142.7, 146.8.
HRMS-EI: m/z [M]+ calcd for C11H12N2OS: 220.0670; found:
220.0670.
3,4-Dihydro-6-methoxy-2H-[1,3]thiazino[3,2-a]benzimidazole
(2¢d)
Brown crystals; mp 118–119 °C.
IR (KBr): 1610, 1587, 1423, 1282 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.36–2.44 (m, 2 H), 3.17 (dd,
J = 5.9, 5.5 Hz, 2 H), 3.90 (s, 3 H), 4.60 (dd, J = 5.9, 5.9 Hz, 2 H),
6.59–6.62 (m, 1 H), 7.08 (dd, J = 8.1, 8.1 Hz, 1 H), 7.21 (dd, J = 8.1,
0.9 Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 23.9, 25.6, 45.5, 55.6, 102.9,
111.3, 122.3, 125.0, 144.6, 146.1, 146.5.
3,4-Dihydro-9-methyl-2H-[1,3]thiazino[3,2-a]benzimidazole
(2b)
Colorless crystals; mp 78–79 °C.
HRMS-EI: m/z [M]+ calcd for C11H12N2OS: 220.0670; found:
220.0677.
IR (KBr): 1598, 1430, 1400, 1309 cm–1.
3,4-Dihydro-8-fluoro-2H-[1,3]thiazino[3,2-a]benzimidazole
(2e)
Colorless solid; mp 144–145 °C.
IR (KBr): 1475, 1432, 1400, 1137 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.46–2.51 (m, 2 H), 3.23 (t,
J = 5.6 Hz, 2 H), 4.18 (dd, J = 6.1, 5.9 Hz, 2 H), 6.93 (ddd, J = 9.0,
8.9, 2.3 Hz, 1 H), 7.12 (dd, J = 8.9, 4.4 Hz, 1 H), 7.33 (dd, J = 9.5,
2.3 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 2.37–2.45 (m, 2 H), 2.61 (s, 3 H),
3.17 (dd, J = 5.7, 5.5 Hz, 2 H), 4.10 (dd, J = 6.1, 5.9 Hz, 2 H), 6.70–
7.09 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 16.6, 23.3, 25.8, 42.5, 105.2,
121.3, 122.7, 127.8, 135.3, 141.9, 145.9.
HRMS-EI: m/z [M]+ calcd for C11H12N2S: 204.0721; found:
204.0719.
13C NMR (150 MHz, CDCl3): d = 23.3, 25.7, 42.6, 104.3 (d,
J = 24.2 Hz), 107.7 (d, J = 9.9 Hz), 109.2 (d, J = 26.4 Hz), 132.2,
143.3 (d, J = 13.2 Hz), 148.3, 159.5 (d, J = 237.1 Hz).
HRMS-EI: m/z [M]+ calcd for C10H9FN2S: 208.0470; found:
208.0472.
3,4-Dihydro-8-methyl-2H-[1,3]thiazino[3,2-a]benzimidazole
(2c)
Colorless crystals; mp 129–130 °C.
IR (KBr): 1591, 1432, 1391, 1270 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.38–2.43 (m, 2 H), 2.44 (s, 3 H),
3.17 (dd, J = 5.6, 5.5 Hz, 2 H), 4.09 (dd, J = 6.1, 5.9 Hz, 2 H), 6.97
(d, J = 7.9 Hz, 1 H), 7.04–7.06 (m, 1 H), 7.38 (s, 1 H).
13C NMR (150 MHz, CDCl3): d = 21.5, 23.2, 25.0, 42.3, 117.8,
122.0, 122.5, 131.8, 133.6, 142.9, 146.5.
3,4-Dihydro-6-fluoro-2H-[1,3]thiazino[3,2-a]benzimidazole
(2¢e)
Colorless crystals; mp 119–120 °C.
IR (KBr): 1494, 1423, 1398, 1274 cm–1.
Synthesis 2011, No. 20, 3235–3240 © Thieme Stuttgart · New York

PAPER
Hypervalent Iodine-Mediated Benzimidazole-Fused Synthesis
3239
1H NMR (600 MHz, CDCl3): d = 2.45–2.50 (m, 2 H), 3.23 (dd,
J = 5.6, 5.6 Hz, 2 H), 4.51 (dd, J = 5.9, 5.9 Hz, 2 H), 6.85 (dd,
J = 11.4, 8.1 Hz, 1 H), 7.09 (ddd, J = 8.1, 8.1, 5.0 Hz, 1 H), 7.34 (d,
J = 8.1 Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 23.6, 25.6, 45.0, 107.6 (d,
J = 17.6 Hz), 114.1 (d, J = 4.4 Hz), 122.2 (d, J = 6.6 Hz), 123.5 (d,
J = 9.9 Hz), 145.9 (d, J = 3.3 Hz), 147.5, 148.5 (d, J = 244.8 Hz).
3,4-Dihydro-7-methyl-2H-[1,3]oxazino[3,2-a]benzimidazole
(6b)
Colorless crystals; mp 136–138 °C.
IR (KBr): 1625, 1546, 1498, 1309 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.17–2.26 (m, 2 H), 2.43 (s, 3 H),
4.02 (dd, J = 6.2, 6.2 Hz, 2 H), 4.46 (dd, J = 6.2, 4.2 Hz, 2 H), 6.92
(s, 1 H), 7.01 (d, J = 8.1 Hz, 1 H), 7.40 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.2, 21.6, 39.5, 66.6, 107.9,
117.4, 123.2, 130.3, 133.0, 137.6, 154.2.
HRMS-EI: m/z [M]+ calcd for C10H9FN2S: 208.0470; found:
208.0468.
HRMS-EI: m/z [M]+ calcd for C11H12N2O: 188.0950; found:
188.0942.
3,4-Dihydro-7-methyl-2H-[1,3]thiazino[3,2-a]benzimidazole
(2f)
Colorless crystals; mp 184–186 °C.
IR (KBr): 1681, 1434, 1405 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.45 (s, 3 H), 2.37–2.48 (m, 2 H),
3.14–3.20 (m, 2 H), 4.08 (dd, J = 5.9, 5.9 Hz, 2 H), 6.97 (s, 1 H),
7.02 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 8.2 Hz, 1 H).
5H-Benzimidazo[1,2-a][3,1]benzoxazine (6c)
Colorless crystals; mp 88–89 °C.
IR (KBr): 1618, 1562, 1467 cm–1.
1H NMR (600 MHz, CDCl3): d = 5.40 (s, 2 H), 7.24–7.33 (m, 4 H),
7.51 (dd, J = 7.9, 7.4 Hz, 1 H), 7.67 (d, J = 7.4 Hz, 1 H), 7.76–7.80
(m, 2 H).
13C NMR (150 MHz, CDCl3): d = 69.1, 111.4, 114.2, 119.3, 121.3,
122.3, 123.4, 125.1, 125.8, 129.8, 130.2, 133.4, 141.1, 155.1.
13C NMR (75 MHz, CDCl3): d = 21.6, 23.4, 25.7, 42.4, 107.8,
117.4, 123.6, 131.3, 135.7, 140.8, 145.9.
Anal. Calcd for C11H12N2S: C, 64.67; H, 5.92; N, 13.71. Found: C,
64.71; H, 6.14; N, 13.31.
HRMS-EI: m/z [M]+ calcd for C14H10N2O: 222.0793; found:
222.0784.
3,4-Dihydro-7-methoxy-2H-[1,3]thiazino[3,2-a]benzimidazole
(2g)
Pyrido[1,2-a]benzimidazole (8a)10
Brown crystals; mp 169–171 °C.
IR (KBr): 1618, 1589, 1438, 1214 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.40–2.45 (m, 2 H), 3.17 (dd,
J = 5.8, 5.5 Hz, 2 H), 3.83 (s, 3 H), 4.06 (dd, J = 6.1, 5.8 Hz, 2 H),
6.65 (d, J = 2.4 Hz, 1 H), 6.83 (dd, J = 8.6, 2.4 Hz, 1 H), 7.47 (d,
J = 8.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 23.4, 25.7, 42.5, 55.8, 92.3,
110.5, 118.2, 136.0, 137.1, 145.2, 155.6.
HRMS-EI: m/z [M]+ calcd for C11H12N2OS: 220.0670; found:
220.0672.
1H NMR (300 MHz, CDCl3): d = 6.86 (ddd, J = 6.9, 6.9, 0.8 Hz, 1
H), 7.35–7.45 (m, 2 H), 7.54 (ddd, J = 8.2, 7.2, 1.0 Hz, 1 H), 7.70
(d, J = 9.2 Hz, 1 H), 7.90 (d, J = 8.3 Hz, 1 H), 7.95 (d, J = 8.3 Hz, 1
H), 8.46 (d, J = 6.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 110.3, 110.4, 118.0, 119.9, 121.0,
125.2, 125.7, 129.3, 129.5, 144.4, 148.5.
8-Methylpyrido[1,2-a]benzimidazole (8b)11
1H NMR (300 MHz, CDCl3): d = 2.56 (s, 3 H), 6.77 (ddd, J = 6.7,
6.7, 1.2 Hz, 1 H), 7.31–7.37 (m, 2 H), 7.61–7.66 (m, 2 H), 7.81 (d,
J = 8.4 Hz, 1 H), 8.33 (ddd, J = 6.9, 1.2, 1.2 Hz, 1 H).
2,3-Dihydrothiazolo[3,2-a]benzimidazole (4a)8
1H NMR (300 MHz, CDCl3): d = 3.90 (dd, J = 7.3, 7.1 Hz, 2 H),
4.25 (dd, J = 7.3, 7.1 Hz, 2 H), 7.15–7.26 (m, 3 H), 7.58–7.62 (m, 1
H).
13C NMR (75 MHz, CDCl3): d = 34.6, 43.7, 108.7, 118.7, 121.7,
121.8, 133.7, 149.3, 158.6.
13C NMR (75 MHz, CDCl3): d = 21.8, 110.0, 110.1, 117.9, 119.4,
125.0, 127.4, 128.7, 128.8, 131.1, 142.6, 148.2.
Dipyrido[1,2-a:2¢,3¢-d]imidazole (8c)12
1H NMR (300 MHz, CDCl3): d = 6.93 (dt, J = 6.8, 0.8 Hz, 1 H),
7.26 (dd, J = 8.1, 4.7, 1 H), 7.50 (ddd, J = 9.2, 6.8, 1.2 Hz, 1 H),
7.75 (d, J = 9.2 Hz, 1 H), 8.22 (dd, J = 8.1, 1.5 Hz, 1 H), 8.50 (d,
J = 6.8 Hz, 1 H), 8.78 (dd, J = 4.7, 1.5 Hz, 1 H).
2,3-Dihydro-6-methylthiazolo[3,2-a]benzimidazole (4b)
Colorless crystals; mp 141–142 °C.
IR (KBr): 1614, 1477, 1392, 1251 cm–1.
13C NMR (75 MHz, CDCl3): d = 111.2, 115.8, 118.0, 118.7, 121.0,
125.8, 130.7, 148.5, 149.4, 156.0.
1H NMR (300 MHz, CDCl3): d = 2.43 (s, 3 H), 3.85 (dd, J = 7.2, 7.2
Hz, 2 H), 4.12 (dd, J = 7.2, 7.2 Hz, 2 H), 6.94 (s, 1 H), 6.99 (d,
J = 8.1 Hz, 1 H), 7.46 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.7, 34.7, 43.7, 109.0, 118.2,
123.2, 131.6, 133.8, 147.4, 157.9.
References
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