A facile and practical solvent-free one-pot synthesis of (Z)-4-methylene-3-selenaquinoline derivatives from o-ethynylanilines and isoselenocyanates

Article abstract of DOI:10.1055/s-0030-1258171

Heating of o-ethynylanilines with isoselenocyanates directly resulted in the 6-exo-dig mode ring-closure reaction of the adducts to give the (Z)-2-imino-4-methylene-3-selenaquinolines in moderate to good yields. Based on this convenient, solvent-free, catalyst-free method, several 3-selenaquinoline derivatives (3,1-benzoselenazines) were easily obtained in one pot. Successful application of the microwave-assisted synthesis of these compounds was also investigated. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258171

PAPER
3091
A Facile and Practical Solvent-Free One-Pot Synthesis of (Z)-4-Methylene-3-
selenaquinoline Derivatives from o-Ethynylanilines and Isoselenocyanates1
Synthesis of
(
Z
)
-4-
a
Methylene
-
r
3-selena
u
quinoline
D
e
k
rivative
s
i Sashida,*a Chao Pan,a Mamoru Kaname,a Mao Minourab
a
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa 920-1181, Japan
E-mail: h-sashida@hokuriku-u.ac.jp
b
Department of Chemistry, School of Science, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
Received 20 April 2010; revised 11 May 2010
workers.11 1,3-Selenazolidines were also obtained by the
reaction of isoselenocyanates and the propargylamines12
or nitrile compounds.13
Abstract: Heating of o-ethynylanilines with isoselenocyanates di-
rectly resulted in the 6-exo-dig mode ring-closure reaction of the ad-
ducts to give the (Z)-2-imino-4-methylene-3-selenaquinolines in
moderate to good yields. Based on this convenient, solvent-free,
catalyst-free method, several 3-selenaquinoline derivatives (3,1-
benzoselenazines) were easily obtained in one pot. Successful ap-
plication of the microwave-assisted synthesis of these compounds
was also investigated.
In the meantime, tandem addition–cyclizations of o-ethynyl-
anilines with the aryl isocyanates14 and isothiocyanates15
were reported by Wu and co-workers in 2008. The former
is a palladium(II) chloride catalyzed reaction to give in-
dole derivatives14 via the 5-endo-dig mode cyclization of
the adducts. The latter provided the synthesis of the 1,3-
benzothiazines15 by the silver-catalyzed reaction of
anilines and also, mainly, aryl isothiocyanates.
Key words: o-ethynyaniline, isoselenocyanate, 3-selenaquinoline,
6-exo mode cyclization, microwave
On the other hand, we have previously disclosed the syn-
theses of selenium-containing heterocycles using in-
tramolecular ring closure of selenols, which were
generated by the reaction of aryl (alkyl) halides with sodi-
um hydrogen selenide (NaHSe) or aryllithium and ele-
mental selenium, with an ethynyl moiety as the synthetic
strategy.16 Very recently, the intramolecular cyclization of
alkyneselenols, generated in situ from selenolactones and
ethynyllithium, was also reported.17 In this paper, we now
describe the practical solvent-free, catalyst-free, one-pot
preparation of selenaquinoline derivatives by intramolec-
ular cyclization of selenols, which used isoselenocyanates
as the selenium source.
Selenium-containing heterocycles are of significant gen-
eral interest not only because of their attractive chemical
properties and reactivities, but also because of their phar-
maceutical applications.2 In particular, 1,3-selenazines,3
which are six-membered heterocyclic compounds con-
taining two heteroatoms, nitrogen and selenium, display
significant antibacterial activity against both Gram-nega-
tive and Gram-positive bacteria and potential anti-tumor
effects against human cancer cell. In general, it is difficult
to construct the six-membered 1,3-selenazine skeleton.
Monocyclic 1,3-selenazines have been mainly prepared
using selenoamides,4 selenoureas5 or related compounds.6
To the best of our knowledge, only three papers7 are avail-
able on the synthesis of the benzene-ring-fused 4-selena-
isoquinoline derivatives, which were obtained by
cyclization of o-selenocyanatobenzoyl chloride with HCl.
However, there is no report on the preparation of their iso-
mers, i.e., 3-selenaquinolines.
Isoselenocyanates,8 which are easy to prepare and are rel-
atively stable and safe to handle and store, have recently
been used as a powerful tool for the synthesis of various
selenium-containing heterocycles. It has been shown that
the reaction of bifunctional nucleophiles with isoseleno-
cyanates produced several five- to seven-membered sele-
nium-containing heterocycles. For examples, Koketsu
and co-workers have described the synthesis of 2-imino-
1,3-oxaselenolanes9 and 1,3-oxaselenepanes10 by the re-
actions of isoselenocyanates with 2-bromoethanol and 4-
bromobutanol, respectively. The synthesis of the 1,3-sel-
enazepanes using isoselenocyanates and 5-chlorobutyl-
amines has been reported by Heimgartner and co-
A preliminary survey to optimize the reaction conditions
was first carried out. One mole of the o-ethynylaniline 1a
with a butyl group at the triple bond was refluxed with 1.2
equivalents of cyclohexyl isoselenocyanate (2A), the sec-
ondary aliphatic isoselenocyanate, in benzene (5 mL) for
72 hours to afford the 2-imino-3-selenaquinoline 3Aa in
only 2% yield. The starting material was recovered in
36% yield along with an unidentified complex mixture
(Table 1, entry 1). When 1a was similarly heated under re-
fluxed conditions in nonpolar solvents, such as toluene,
xylene, or mesitylene, the desired compound 3Aa was iso-
lated in 8–27% yields. An increase in the reaction temper-
ature tends to increase the yields of the products, while
refluxing in mesitylene (~160 °C) produced 3Aa in a low
yield due to the instability of the isoselenocyanate 2A (en-
tries 2–4).
The addition of triethylamine in o-xylene also did not give
a good result (entry 5). The use of polar solvents, e.g., py-
ridine, dioxane, DMF, and DMSO, at 100 °C or 130 °C re-
duced the yields of the products (entries 6–9). Increasing
the concentration of o-ethynylaniline (1a) by ten times
with cyclohexyl isoselenocyanate (2A) in xylene for 6.5
SYNTHESIS 2010, No. 18, pp 3091–3096
x
x.
x
x
.
2
0
1
0
Advanced online publication: 12.07.2010
DOI: 10.1055/s-0030-1258171; Art ID: F07110SS
© Georg Thieme Verlag Stuttgart · New York

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H. Sashida et al.
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Table 1 Reaction of o-(Hex-1-ynyl)aniline (1a) with Cyclohexyl Isoselenocyanate (2A)
n-Bu
n-Bu
N=C=Se
2A
Se
NH2
N
N
H
1a
3Aa
Entry
Conditions
Substrate concentration (M)a Recoveryb (%)
Yieldb (%)
1
2
benzene, reflux, 72 h
toluene, reflux, 72 h
o-xylene, reflux, 72 h
mesitylene, reflux, 9 h
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
2
36
21
27
46
24
24
22
34
25
-
2
12
27
8
3
4
5
o-xylene, Et3N, reflux, 72 h
pyridine, reflux, 72 h
dioxane, reflux, 72 h
DMF, 130 °C, 31 h
DMSO, 130 °C, 72 h
xylene, 130 °C, 6.5 h
neat, 130 °C, 4 h
3
6
8
7
6
8
1
9
6
10
11
52
88
–
-
a Using substrate 1a (1.0 mmol), 2A (1.2 mmol), and solvent (5 mL), except entries 10 and 11.
b Isolated yield.
hours at 130 °C gave the 3-selenaquinoline 3Aa in 52%
yield (entry 10). Furthermore, the solvent-free reaction of
NCSe
o-ethynylaniline (1a) with isoselenocyanate 2A at 130 °C
afforded 3Aa in 88% yield as the sole product (entry 11).
2A
1a
3Aa
6-exo-dig
A possible mechanism for the formation of 2-imino-3-se-
lenaquinoline 3Aa from o-ethynylaniline (1a) with isose-
lenocyanate 2A is shown in Scheme 1. The initial adduct,
1-cyclohexyl-3-phenylselenourea 4, undergoes tautomer-
n-Bu
n-Bu
SeH
Se
ism to form the iminoselenol 5. The regio- and stereose-
N
H
N
H
N
N
lective intramolecular cyclization of the resulting selenol
5 with the triple bond proceeds via the 6-exo-dig mode to
give the successful 3-selenaquinoline 3. No 7-endo-dig
mode cyclization products 6 or 7 were obtained in this
case.
H
5
4
7-endo-dig
n-Bu
n-Bu
Se
Next, the extension of this tandem addition–ring closure
reaction of the o-ethynylanilines 1b–f having an alkyl,
phenyl, or trimethylsilyl group at the ethynyl moiety and
a few types of isoselenocyanates 2B–D was carried out
(Table 2). The o-ethynylaniline (1a) was similarly re-
fluxed with 1.2 equivalents of butyl isoselenocyanate
(2B), the primary aliphatic isoselenocyanate, in xylene
(method I) for 22 hours to give the desired (butylimino)-
3-selenaquinoline 3Ba in 44% yield (entry 3). The reac-
tion of 1a with isoselenocyanate 2B under solvent-free
conditions (method II) gave 3Ba in 62% yield (entry 4).
However, tert-butyl isoselenocyanate (2C), a tertiary ali-
phatic isoselenocyanate, reacted with o-ethynylaniline
(1a) under both the conditions of methods I and II to give
a complex mixture without producing any characterized
Se
or
N
H
N
N
N
H
6
7
Scheme 1
products (entries 5 and 6). When the o-ethynylaniline (1a)
was heated with phenyl isoselenocyanate (2D) under the
conditions of methods I and II to give 2-(phenylimino)-3-
selenaquinoline 3Da in 33% and 41% yields, respectively
(entries 7 and 8). Therefore, the reaction of the several
types of o-ethynylanilines 1b–f with cyclohexyl isosele-
nocyanate (2A) under the conditions of method II was
Synthesis 2010, No. 18, 3091–3096 © Thieme Stuttgart · New York

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Synthesis of (Z)-4-Methylene-3-selenaquinoline Derivatives
3093
next examined. In these cases, the 2-(cyclohexyimino)-3- spite of higher electrophilicity than that of the primary
selenaquinolines 3Ab–f with an alkylidene or ben- anilines 1. Similarly, the steric bulky tert-butyl isoseleno-
zylidene group at C4 were produced in moderate yields cyanate (2C) decomposed under the same conditions
(entries 9–13), and the 2-(phenylimino)-3-selenaquino- without forming the corresponding adducts.
line 3Dd was also obtained in 87% yield by using phenyl
isoselenocyanate (2D) instead of 2A (entry 14). In con-
trast, both the N-methyl- 8a and N-benzyl-o-ethynyl-
anilines (9a) did not react with the isoselenocyanates 2 to
produce the corresponding 3-selenaquinolines 10 and 11.
The first step, the nucleophilic addition of the anilines 8
and 9 to the isoselenocyanates 2A–D did not occur under
the conditions of method I; the starting isoselenocyanates
2A–D were recovered (entries 15 and 16). The secondary
amines 8 and 9 may be unable to attack the sp carbon of
the isoselenocyanate 2 due to steric hindrance of the N-
substituent and ethynyl moiety at the ortho position in
On the other hand, solvent-free18 and microwave-assisted
synthesis19 has gained popularity in recent years, by re-
ducing the reaction time from hours to minutes and in-
creasing the yields. Thus, this construction of the 3-
selenaquinoline framework was finally successfully at-
tempted using the microwave synthesis instead of tradi-
tional heating in the solvent or solvent-free systems
(method I or II) described above. After several unsuccess-
ful evaluations of the method, we determined the opti-
mized reaction conditions. The results obtained by the
microwave irradiation are summarized in Table 3. These
results clearly indicate the following benefits: (1) this mi-
Table 2 4-Methylene-3-selenaquinolines 3
R1
R1
R2 N=C=Se
2
Se
R2
NHX
N
X
N
a R1 = n-Bu A R2 = c-Hex
1 X = H
8 X = Me
9 X = Bn
3 X = H
10 X Me
11 X = Bn
b R1 = Me
c R1 = t-Bu
d R1 = Ph
e R1 = TMS
f R1 = H
B R2 = n-Bu
C R2 = t-Bu
D R2 = Ph
Entry
1
X
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Bn
R1
R2
Methoda
Time (h)
6.5
4
Product
3Aa
3Aa
3Ba
Yieldb (%)
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Me
t-Bu
Ph
c-Hex
c-Hex
Bu
I
52
88
44
62
0c
2
II
3
I
22
7
4
Bu
II
3Ba
5
t-Bu
t-Bu
Ph
I
7
3Ca
3Ca
3Da
3Da
3Ab
3Ac
6
II
7
0c
7
I
3.5
3.5
8
43
51
63
53
68
47
51
87
0d
8
Ph
II
9
c-Hex
c-Hex
c-Hex
c-Hex
c-Hex
Ph
II
II
II
II
II
II
II
II
10
11
12
13
14
15
16
11
13
20
16
2.5
20
20
3Ad
3Ae
TMS
H
3Af
Ph
3Dd
10Aa
11Aa
Bu
Bu
c-Hex
c-Hex
0d
a Method I: xylene, reflux; method II: neat, 130 °C.
b Isolated yield.
c Decomposed.
d No reaction.
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The microwave heating was performed in The CEM Focused Mi-
crowaveTM Synthesis System (CEM Corporation). Melting points
were measured on a Yanagimoto micromelting point hot stage ap-
paratus and are uncorrected. IR spectra were recorded on a Horiba
FT-720 spectrophotometer. MS and HRMS spectra were recorded
on a Jeol SX-102A instrument. NMR spectra were recorded on a
Jeol ECP-500 (500 MHz) spectrometer (CDCl3 or DMSO-d6, TMS
internal standard).
All ethynylanilines, o-(hex-1-ynyl)aniline (1a),21 o-(prop-1-
ynyl)aniline (1b),22 o-(3,3-dimethylbut-1-ynyl)aniline (1c),23 o-
(phenylethynyl)aniline (1d),22 o-[(trimethylsilyl)ethynyl]aniline
(1e),23,24 and o-ethynylaniline (1f)22,23 were prepared by literature
methods. Cyclohexyl isoselenocyanate (2A),25 butyl isoselenocyan-
ate (2B),25 tert-butyl isoselenocyanate (2C),25 and phenyl isoseleno-
cyanate (2D)26 were also prepared by literature methods.
crowave reaction efficiently proceeded and was complet-
ed even when the reaction time was reduced from one
hour to almost within 30 minutes; (2) solvent-free system;
and (3) the products were obtained directly by short chro-
matography purification.
Table 3 Microwave Synthesis of 4-Methylene-3-selenaquinolines
3A
R
R
N=C=Se
Se
2A
N
N
NHX
1 X = H
8 X = Me
9 X = Bn
X
3 X = H
10 X Me
11 X = Bn
(Z)-2-Imino-4-methylene-1,2,3,4-tetrahydro-3-selenaquino-
lines 3; General Procedures
Method I: A mixture of aniline 1 (1 mmol) and isoselenocyanate 2
(1.2 mmol) in o-xylene (0.5 mL) was heated at 130 °C for 3.5–22 h.
The mixture was evaporated and the residue was chromatographed
(silica gel) to give 3.
Entry
X
R
Time (min) Product
Yielda (%)
1
2
3
4
5
6
7
8
H
Bu
Me
t-Bu
Ph
25
26
34
48
26
28
40
40
3Aa
3Ab
3Ac
87
54
59
72
53
46
H
Method II: A mixture of aniline 1 (1 mmol) and isoselenocyanate 2
(1.2 mmol) was heated at 130 °C without solvent for 3.5–20 h. The
mixture was chromatographed (silica gel) to give 3.
H
H
3Ad
3Ae
Method III: Aniline 1 (1 mmol), isoselenocyanate 2 (1.2 mmol), and
a stirrer bar were added to a vial microwave tube. The vial was
sealed with a septum and subjected to microwave irradiation at 115
°C for 25–48 min. The mixture was chromatographed (silica gel) to
give 3.
H
TMS
H
H
3Af
Me
Bn
Bu
Bu
10Aa
11Aa
0b
0b
(Z)-2-(Cyclohexylimino)-4-pentylidene-1,2,3,4-tetrahydro-3-
selenaquinoline (3Aa)
Yellow prisms; mp 99–101 °C (n-hexane).
IR (KBr): 3238 (NH), 1603 cm–1 (C=N).
a Isolated yield.
b Decomposed.
1H NMR (500 MHz, CDCl3): d = 0.93 (t, J = 7.3 Hz, 3 H), 1.14–
1.28 (m, 3 H), 1.34–1.52 (m, 6 H), 1.58–1.67 (m, 1 H), 1.70–1.78
(m, 2 H), 2.05–2.14 (m, 2 H), 2.24 (dt, J = 7.2, 7.2 Hz, 2 H), 3.94–
4.05 (m, 1 H) (all HBu and HCy), 4.48–4.67 (br, 1 H, NH), 6.26 (t,
J = 7.2 Hz, 1 H, Holefin), 7.04 (ddd, J = 7.7, 6.4, 1.4 Hz, 1 H), 7.12
(dd, J = 8.0, 1.4 Hz, 1 H), 7.23 (ddd, J = 8.0, 6.4, 1.4 Hz, 1 H), 7.33
(dd, J = 7.7, 1.4 Hz, 1 H) (all HPh).
The structures of these 3-selenaquinoline 3 were elucidat-
1
ed from MS, H and 13C NMR spectra, and elemental
analyses, and finally established by single-crystal X-ray
studies using of phenyl derivative 3Dd (Figure 1).20
13C NMR (125 MHz, CDCl3): d = 14.0 (q), 22.4 (t), 24.9 (t), 25.7 (t),
31.1 (t), 31.3 (t), 33.5 (t), 51.6 (d), 122.1 (s), 123.5 (d), 124.6 (d),
125.3 (s), 126.3 (d), 128.7 (d), 130.8 (d), 146.1 (s), 147.9 (s).
MS (EI): m/z (%) = 362 (M+, 100), 360 (50), 224 (81), 199 (48).
HRMS (EI): m/z [M]+ calcd for C19H26N280Se: 362.1262; found:
362.1269.
(Z)-2-(Butylimino)-4-pentylidene-1,2,3,4-tetrahydro-3-selena-
quinoline (3Ba)
Yellow oil.
IR (neat): 3402 (NH), 1610 cm–1 (C=N).
1H NMR (500 MHz, CDCl3): d = 0.93 (t, J = 7.2 Hz, 3 H), 0.96 (t,
J = 7.3 Hz, 3 H), 1.34–1.51 (m, 6 H), 1.57–1.64 (m, 2 H), 2.24 (dt,
J = 7.2, 7.2 Hz, 2 H), 3.53 (J = 7.1 Hz, 2 H) (all HBu, 2 Bu), 6.26 (t,
J = 7.2 Hz, 1 H, Holefin), 7.05 (ddd, J = 7.7, 7.2, 1.4 Hz, 1 H), 7.14
(dd, J = 8.0, 1.4 Hz, 1 H), 7.23 (ddd, J = 8.0, 7.2, 1.5 Hz, 1 H), 7.34
(dd, J = 7.7, 1.5 Hz, 1 H) (all HPh).
13C NMR (125 MHz, CDCl3): d = 13.8 (q), 14.0 (q), 20.1 (t), 22.4
(t), 31.15 (t), 31.23 (t), 31.8 (t), 42.8 (t), 122.2 (s), 123.7 (d), 124.7
(d), 125.2 (s), 126.4 (d), 128.7 (d), 131.0 (d), 146.1 (s), 148.9 (s).
Figure 1 ORTEP drawing of 3Dd with 50% probability level
In conclusion, we have developed the practical one-pot
preparation of (Z)-methylene-3-selenaquinolines by the
solvent-free, catalyst-free reaction of o-ethynylanilines
and isoselenocyanates.
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Synthesis of (Z)-4-Methylene-3-selenaquinoline Derivatives
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MS (EI): m/z = 336 (M+, 100), 334 (51), 293 (38), 255 (59), 227
(42), 224 (38).
HRMS (EI): m/z [M]+ calcd for C17H24N280Se: 336.1105; found:
336.1104.
1H NMR (500 MHz, CDCl3): d = 1.07–1.24 (m, 3 H), 1.30–1.45 (m,
2 H), 1.54–1.78 (m, 3 H), 1.96–2.10 (m, 2 H), 3.92–4.04 (m, 1 H)
(all HCy), 4.29–4.60 (br, 1 H, NH), 7.06–7.14 (m, 1 H), 7.17 (dd,
J = 8.0, 1.4 Hz, 1 H), 7.22–7.43 (m, 7 H), 7.45 (dd, J = 7.9, 1.5 Hz,
1 H) (all Holefin and HPh).
(Z)-4-Pentylidene-2-(phenylimino)-1,2,3,4-tetrahydro-3-selena-
quinoline (3Da)
Orange prisms; mp 102–104 °C (n-hexane).
13C NMR (125 MHz, CDCl3): d = 24.7 (t), 25.6 (t), 33.3 (t), 51.4 (d),
122.2 (s), 123.6 (d), 125.9 (d), 126.5 (d), 127.6 (s), 127.7 (d), 128.1
(d), 129.1 (d), 129.4 (d), 129.8 (d), 137.0 (s), 146.0 (s), 147.2 (s).
IR (KBr): 3434 (NH), 1631 cm–1 (C=N).
MS (EI): m/z = 382 (M+, 100), 380 (50), 300 (60), 299 (41), 220
(52), 219 (92).
1H NMR (500 MHz, CDCl3): d = 0.89 (t, J = 7.3 Hz, 3 H), 1.28–
1.38 (m, 2 H), 1.38–1.47 (m, 2 H), 2.18 (dt, J = 7.2, 7.2 Hz, 2 H) (all
HBu), 3.31–3.98 (br, 1 H, NH), 6.24 (t, J = 7.2 Hz, 1 H, Holefin), 6.90
(d, J = 8.0 Hz, 1 H), 7.02 (ddd, J = 7.8, 6.4, 1.3 Hz, 1 H), 7.09–7.17
(m, 2 H), 7.25–7.30 (m, 2 H), 7.30–7.36 (m, 3 H) (all HPh).
13C NMR (125 MHz, CDCl3): d = 14.0 (q), 22.3 (t), 31.1 (t), 31.2 (t),
121.9 (d), 122.2 (d), 123.0 (s), 123.5 (d), 124.0 (s), 124.1 (d), 125.0
(d), 128.7 (d), 129.0 (d), 131.9 (d), 141.4 (s), 144.3 (s), 148.8 (s).
HRMS (EI): m/z [M]+ calcd for C21H22N280Se: 382.0949; found:
382.0956.
(Z)-2-(Cyclohexylimino)-4-[(trimethylsilyl)methylene]-1,2,3,4-
tetrahydro-3-selenaquinoline (3Ae)
Orange oil.
IR (neat): 3338 (NH), 1614 cm–1 (C=N).
MS (EI): m/z = 356 (M+, 72), 354 (37), 300 (40), 275 (100), 231
(45).
HRMS (EI): m/z [M]+ calcd for C19H20N280Se: 356.0793; found:
356.0792.
1H NMR (500 MHz, CDCl3): d = 0.23 (s, 9 H, TMS), 1.14–1.27 (m,
3 H), 1.33–1.46 (m, 2 H), 1.58–1.66 (m, 1 H), 1.68–1.77 (m, 2 H),
2.03–2.13 (m, 2 H), 3.89–4.01 (m, 1 H) (all HCy), 4.23–4.94 (br, 1
H, NH), 6.56 (s, 1 H, Holefin), 7.03 (ddd, J = 7.6, 7.4, 1.4 Hz, 1 H),
7.10 (dd, J = 8.0, 1.4 Hz, 1 H), 7.21–7.26 (m, 1 H), 7.44 (dd, J = 7.6,
1.4 Hz, 1 H) (all HPh).
13C NMR (125 MHz, CDCl3): d = –0.42 (q), 24.8 (t), 25.6 (t), 33.5
(t), 51.8 (d), 123.1 (s), 123.6 (d), 124.0 (d), 126.6 (d), 129.5 (d),
130.8 (d), 141.3 (s), 145.9 (s), 148.6 (s).
MS (EI): m/z = 378 (M+, 100), 376 (52), 296 (55), 281 (47), 215
(85), 73 (67).
HRMS (EI): m/z [M]+ calcd for C18H26N280Se: 378.1031; found:
378.1029.
(Z)-2-(Cyclohexylimino)-4-ethylidene-1,2,3,4-tetrahydro-3-
selenaquinoline (3Ab)
Yellow oil.
IR (neat): 3392 (NH), 1610 cm–1 (C=N).
1H NMR (500 MHz, CDCl3): d = 1.11–1.24 (m, 3 H), 1.33–1.44 (m,
2 H), 1.57–1.64 (m, 1 H), 1.67–1.75 (m, 2 H), 2.02–2.13 (m, 2 H),
3.93–4.04 (m, 1 H) (all HCy), 1.86 (d, J = 6.8 Hz, 3 H, CH3), 4.50–
4.78 (br, 1 H, NH), 6.30 (q, J = 6.8 Hz, 1 H, Holefin), 7.02 (ddd,
J = 7.7, 7.1, 1.1 Hz, 1 H), 7.13 (dd, J = 8.0, 1.1 Hz, 1 H), 7.22 (ddd,
J = 8.0, 7.1, 1.3 Hz, 1 H), 7.31 (dd, J = 7.7, 1.3 Hz, 1 H) (all HPh).
(Z)-2-(Cyclohexylimino)-4-methylene-1,2,3,4-tetrahydro-3-
selenaquinoline (3Af)
Yellow oil.
IR (neat): 3384 (NH), 1614 cm–1 (C=N).
13C NMR (125 MHz, CDCl3): d = 16.9 (q), 24.9 (t), 25.6 (t), 33.4 (t),
51.6 (d), 122.1 (s), 123.5 (d), 124.5 (d), 124.9 (d), 126.3 (d), 126.5
(s), 128.7 (d), 146.0 (s), 147.7 (s).
MS (EI): m/z = 320 (M+, 60), 318 (31), 238 (45), 236 (23), 158
(100), 130 (35).
HRMS (EI): m/z [M]+ calcd for C16H20N280Se: 320.0792; found:
320.0793.
1H NMR (500 MHz, CDCl3): d = 1.14–1.28 (m, 3 H), 1.34–1.47 (m,
2 H), 1.59–1.68 (m, 1 H), 1.70–1.78 (m, 2 H), 2.04–2.12 (m, 2 H),
3.90–4.02 (m, 1 H) (all HCy), 4.25–4.85 (br, 1 H, NH), 5.40 and 5.99
(each d, J = 1.1 Hz, 1 H, Holefin), 7.06 (ddd, J = 8.0, 7.2, 1.4 Hz, 1
H), 7.14 (dd, J = 8.0, 1.1 Hz, 1 H), 7.24–7.29 (m, 1 H), 7.46 (dd,
J = 7.7, 1.1 Hz, 1 H) (all HPh).
13C NMR (125 MHz, CDCl3): d = 24.8 (t), 25.6 (t), 33.5 (t), 51.7 (d),
115.4 (t), 120.9 (s), 123.59 (d), 123.63 (d), 126.6 (d), 129.7 (d),
133.2 (s), 146.4 (s), 148.1 (s).
MS (EI): m/z = 306 (M+, 38), 224 (63), 196 (63), 144 (98), 116 (95),
55 (100).
HRMS (EI): m/z [M]+ calcd for C15H18N280Se: 306.0636; found:
306.0640.
(Z)-2-(Cyclohexylimino)-4-(2,2-dimethylpropylidene)-1,2,3,4-
tetrahydro-3-selenaquinoline (3Ac)
Yellow oil.
IR (neat): 3435 (NH), 1608 cm–1 (C=N).
1H NMR (500 MHz, CDCl3): d = 1.10 (s, 9 H, t-Bu), 1.15–1.24 (m,
3 H), 1.33–1.45 (m, 2 H), 1.58–1.66 (m, 1 H), 1.68–1.77 (m, 2 H),
2.04–2.13 (m, 2 H), 3.90–4.00 (m, 1 H) (all HCy), 4.18–4.92 (br, 1
H, NH), 6.00 (s, 1 H, Holefin), 6.99 (ddd, J = 8.0, 7.4, 1.3 Hz, 1 H),
7.10 (dd, J = 8.0, 1.1 Hz, 1 H), 7.22 (ddd, J = 7.7, 7.4, 1.1 Hz, 1 H),
7.31 (dd, J = 7.7, 1.3 Hz, 1 H) (all HPh).
13C NMR (125 MHz, CDCl3): d = 24.8 (t), 25.6 (t), 31.0 (q), 33.5 (t),
35.7 (s), 51.9 (d), 121.4 (s), 121.7 (d), 124.4 (s, × 2), 124.9 (d),
127.7 (d), 128.8 (d), 148.7 (s), 149.5 (d).
(Z)-4-Benzylidene-2-(phenylimino)-1,2,3,4-tetrahydro-3-
selenaquinoline (3Dd)
Colorless prisms; mp 214–215 °C (CHCl3).
IR (KBr): 3448 (NH), 1626 cm–1 (C=N).
MS (EI): m/z = 362 (M+, 100), 360 (52), 305 (49), 224 (45).
HRMS (EI): m/z [M]+ calcd for C19H26N280Se: 362.1262; found:
1H NMR (500 MHz, DMSO-d6): d = 7.02 (dd, J = 7.3, 7.3 Hz, 1 H),
7.22 (d, J = 8.0 Hz, 2 H), 7.31 (dd, J = 8.2, 7.6 Hz, 2 H), 7.61–7.63
(m, 2 H), 7.79–7.86 (m, 2 H) (all HPh), 7.34–7.48 (m, 6 H, HPh,
362.1251.
Holefin), 9.57 (s, 1 H, NH).
(Z)-4-Benzylidene-2-(cyclohexylimino)-1,2,3,4-tetrahydro-3-
selenaquinoline (3Ad)
Yellow prisms; mp 146–147 °C (n-hexane).
IR (KBr): 3390 (NH), 1616 cm–1 (C=N).
13C NMR (125 MHz, DMSO-d6): d = 119.5 (d), 121.6 (s), 122.6 (d),
124.5 (d), 125.7 (d), 126.7 (s), 127.8 (d), 128.2 (d), 128.3 (d), 128.7
(d), 129.0 (d), 129.5 (d), 130.3 (d), 136.6 (s), 140.5 (s), 144.1 (s),
144.9 (s).
Synthesis 2010, No. 18, 3091–3096 © Thieme Stuttgart · New York

3096
H. Sashida et al.
PAPER
MS (EI): m/z = 376 (M+, 70), 295 (100), 193 (10), 77 (10).
HRMS (EI): m/z [M]+ calcd for C21H16N280Se: 376.0479; found:
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376.0479.
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Acknowledgment
This work was supported in part by a Grant-in Aid for Scientific Re-
search from the Ministry of Education, Science and Culture, Japan
(19590022).
(14) Ye, S.; Ding, Q.; Wang, Z.; Zhou, H.; Wu, J. Org. Biomol.
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Synthesis 2010, No. 18, 3091–3096 © Thieme Stuttgart · New York