5-N-Arylaminothiazoles as Highly Twisted Fluorescent Monocyclic Heterocycles: Synthesis and Characterization

Article abstract of DOI:10.1021/acs.joc.5b01963

A series of 5-N-arylaminothiazoles was prepared by reacting thioamide dianions derived from secondary thioamides with thioformamides, followed by sequential oxidation with iodine. X-ray analyses demonstrated that they adopt structures that are highly twis

Full text of DOI:10.1021/acs.joc.5b01963

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Article
5-N-Arylaminothiazoles as Highly Twisted Fluorescent
Monocyclic Heterocycles: Synthesis and Characterization
Kirara Yamaguchi, Toshiaki Murai, Saki Hasegawa, Yohei Miwa, Shoichi
Kutsumizu, Toshifumi Maruyama, Takahiro Sasamori, and Norihiro Tokitoh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01963 • Publication Date (Web): 06 Oct 2015
Downloaded from http://pubs.acs.org on October 11, 2015
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5-N-Arylaminothiazoles as Highly Twisted Fluorescent Monocyclic Heterocycles: Synthesis
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and Characterization
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Kirara Yamaguchi,† Toshiaki Murai,*†,‡ Saki Hasegawa,† Yohei Miwa,† Shoichi Kutsumizu,†
Toshifumi Maruyama,† Takahiro Sasamori,§ and Norihiro Tokitoh§
†Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu
University, Yanagido, Gifu 501-1193, Japan
‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
§Institute for Chemical Research, Kyoto University, Uji 611-0011, Japan
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Abstract: A series of 5-N-arylaminothiazoles were prepared by reacting thioamide dianions
derived from secondary thioamides with thioformamides, followed by sequential oxidation
with iodine. X-ray analyses demonstrated that they adopt structures that are highly twisted
from planar conformations. Their orientations were tuned by the steric and/or electronic
interactions of the substituents at their 2-, 4- and 5-positions. The 5-aminothiazoles
exhibited a range of fluorescent emissions, from blue to orange. While the absorption
spectra were independent of the polarity of the solvent, fluorescent emissions were influenced
by the polarity of the solvent: in more polar solvents, the emissions were red-shifted. These
phenomena were examined in terms of Lippert-Mataga plots and the change in the dipole
moment between the ground and excited states. They also exhibited emissions in a solid
state, again from blue to orange. Cyclic voltammetry of the 5-aminothiazoles showed
reversible waves of one-electron oxidation. The half-potential of the oxidation was reduced
by the introduction of electron-donating groups to the phenyl groups on the nitrogen atom at
the 5-position. DFT calculations were carried out to determine the energy levels of HOMO
and LUMO. Finally, the results of TG-DTA showed that they are thermally stable.
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Substituents
Solvatochromism
DFT Calculation
INTRODUCTION
Monocyclic 1,3-azoles, such as imidazoles, oxazoles, and thiazoles, are potential motifs for
providing fluorescent molecules that can be used in OLED1 and chemosensors.2 Unlike
condensed azoles, monocyclic 1,3-azoles possess a certain level of flexibility. As a result,
the efficiency and wavelength range of fluorescence appear to be low and narrow,
respectively, with single monocyclic units. However, those compounds possess three carbon
atoms to which a wide variety of substituents can be attached. When these substituents are
bulky and aromatic groups, they strongly affect the conformation of the whole molecule,
since the core structural moieties are rather small compared with condensed 1,3-azoles. Due
to the proximity of the introduced substituents in the core structures, they cannot be oriented
in the same plane, but instead adopt twisted three-dimensional structures.3 This feature may
give rise to their unique fluorescent properties.
Furthermore, the introduction of
electron-donating and -attracting groups to the appropriate positions of monocyclic
heteroaromatic compounds provides D-A molecules.4 Therefore, increasing attention has
been paid to fluorescent 1,3-imidazoles,5 oxazoles,6 and thiazoles.7 In this regard, we
recently developed 5-N,N-diarylaminothiazoles8 and –selenazoles9 for the first time in a series
of studies on the chemistry of C=S-10 and C=Se-11 containing compounds. These are rare
examples12 of 1,3-azoles with diarylamino groups attached to the 5-position of 1,3-azoles.
Their synthesis has been achieved with an unprecedented transition-metal-free coupling
reaction between secondary thioamides and thioformamides. This method is in a marked
contrast to the established method for preparing thiazoles using primary thioamides, which is
known as Hantzsch thiazole synthesis.13 The resulting 5-aminothiazoles adopt highly
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deviated conformations, but show strong blue fluorescence. Due to the facile synthetic
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methods and the ready availability of the starting materials,
a
variety of
5-N-arylaminothiazoles can be obtained. We report herein the synthesis and characteristic
photophysical, electrochemical, and thermal properties of a series of 5-N-arylaminothiazoles.
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RESULTS AND DISCUSSION
Syntheses
For the synthesis of a 5-aminothiazole library, 5-amino-2-thiazolines were prepared by
reacting secondary thioamides 1 with thioformamides 3. The results are summarized in
Table 1. First, thioamide dianion 2a14 was generated from secondary thioamide 1a by
treatment with n-BuLi (2 equiv) at 0 °C. As an electrophile, N,N-diphenyl thioformamide
(3a) was added to the reaction mixture, followed by the addition of iodine (3 equiv) to give
trans-5-diphenylamino-2-thiazoline 4 in 97% yield (entry 1). A similar reaction enabled the
introduction of a range of substituents to the 2-, 4-, and 5-positions. The reactions of
thioamides 1b−e and thioformamide 3a gave 2-thiazolines 5–8 having 4-chlorophenyl-,
2-pyridyl-, 4-pyridyl- and biphenyl groups at the 2 position in good yields (entries 2−5). A
variety of aromatic substituents were introduced to the 4-positions with the use of
N-arylmethyl thioamides 1f−1h to form 9–11 (entries 6−8). 4-Styryl-2-thiazoline 12 was
obtained with N-cinnamyl thioamide 1i and s-BuLi to generate the corresponding dianion 2i
(entry 9). Compounds with a wide variety of substituents on the nitrogen atoms were
prepared. The use of N-benzyl, N-phenyl thioformamide (3b) led to 2-thiazolines 13−15
(entries 10−12). An adamantyl group on the nitrogen atom was successfully introduced with
thioformamide 3c to give 17–18 (entries 13–15). However, in the reaction of thioamide 1a,
the desired product 16 was scarcely obtained, and instead thiazole 17, probably formed by the
oxidation of 16, was isolated in 19% yield (entry 13). In contrast, the reaction of thioamide
dianions, generated from 1b and 1c with n-BuLi, with 3d yielded the corresponding
2-thiazolines 18 and 19 in respective yields of 50% and 31% (entries 14 and 15). Finally,
5-N-arylamino-2-thiazolines 20–24 with electron-donating groups such as 4-methyl-,
4-methoxy- and 4-dimethylaminophenyl groups on the nitrogen atom at the 5-position were
also obtained in 58–72% yields (entries 16–20).
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Table 1. Synthesis of 5-amino-2-thiazolines 4-24a
S
R
5
6
7
8
H
N
I2
R
N
3
R'
LiS
Ar
Li
S
n-BuLi (2 equiv)
(1 equiv)
(2-3 equiv)
S
N
R'
N
Ar'
Ar
N
Ar'
Ar
4-24
0 or rt, 2-3 h
9
0 °C, 0-0.5 h
THF, 0 °C, 10 min
H
2
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12
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1
Ar'
yield(%)b
64
yield(%)b
97
entry
1
3
product
entry
1
1
3
product
Ph
Bn
N
N
Ar = 4-Py
Ar' = Ph
1d
R = Bn
R' = Ph
3c
S
N
S
N
Ph
Ph
Ar = Ar' = Ph
R = R' = Ph
12
Ph
4-Py
15
1a
3a
4
Ph
Ph
Ph
N
1-Adm
N
Ar = 4-ClC6H4
Ar' = Ph
1b
R = 1-adamantyl
R' = Ph
S
N
S
N
4c,d
Ph
Ph
2
3
4
5
63
66
80
60
13 Ar = Ar' = Ph
4-ClC6H4
Ph
1a
3d
16
5
Ph
Ph
Ph
1-Adm
N
N
Ar = 2-Py
Ar' = Ph
1c
S
S
N
19c
Ph
Ph
2-Py
Ph
N
6
17
Ph
Ph
N
Ph
1-Adm
N
Ar = 4-Py
Ar' = Ph
Ar = 4-ClC6H4
Ar' = Ph
S
N
S
N
Ph
Ph
14
50
31
4-Py
4-ClC6H4
18
1b
1d
7
Ph
Ph
Ph
N
1-Adm
N
Ar = 4-PhC6H4
Ar' = Ph
Ar = 2-Py
15
S
N
S
Ph
Ph
Ar' = Ph
4-PhC6H4
2-Py
1c
1e
N
8
19
Ph
Ph
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Ph
N
N(C6H4Me-4)2
Ph
S
N
R, R'
= 4-MeC6H4
Ar = Ph
Ar' = C6H4Me-2
S
N
Ph
Ph
20
16 Ar = Ar' = Ph
71
6
7
8
50
92
34
Ph
1a
3e
1f
9
C6H4Me-2
Ph
N(C6H4Me-4)2
S
N
N
Ar = 4-PhC6H4
Ar' = Ph
10
11
12
13
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Ar = Ph
Ar' = C6H4OMe-2
S
Ph
4-PhC6H4
17
72
Ph
10
Ph
21
1e
1g
N
C6H4OMe-2
Ph
N(C6H4OMe-4)2
62
S
N
N
R, R'
= C6H4OMe-4
Ar = 4-ClC6H4
Ar' = C6H4OMe-2
1h
S
N
Ph
Ph
18 Ar = Ar' = Ph
4-ClC6H4
11
Ph
22
1a
3b
C6H4OMe-2
Ph
N
N(C6H4NMe2-4)2
S
N
S
Ph
R, R'
= C6H4NMe2-4
Ar = Ph
Ar' = CH=CHPh
Ph
19 Ar = Ar' = Ph
58
9
30
Ph
12
N
Ph
23
1a
3f
1i
Ph
Bn
N(C6H4NMe2-4)2
S
N
N
Ar = 4-PhC6H4
Ar' = Ph
Ar = 4-PhC6H4
Ar' = Ph
1e
R = Bn
R' = Ph
3c
S
4-PhC6H4
24
20
66
Ph
10
40
58
4-PhC6H4
Ph
1e
N
13
Ph
Bn
N
Ar = 2-Py
Ar' = Ph
1c
S
N
Ph
11
2-Py
14
Ph
aThe reaction was carried out as follows, unless otherwise noted : To a solution of thioamide 1 (1.0 equiv) in THF (2.0 mL) was slowly added n-
BuLi (2.0 equiv), and the mixture was stirred. To this was added thioformamide 3 (1.0 equiv), and the mixture was stirred. To this was added
iodine (2.0 or 3.0 equiv), and the mixture was stirred. bIsolated yields. cThe reaction of 1a and 3d gave thiazole 18 as the main product in 19%
yield. dNot isolated.
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Oxidation of the resulting 2-thiazolines 4–15 and 18–24 was carried out with iodine as an
oxidant (Table 2). The time required for the reaction to run to completion was dependent on
the substituents attached to the thiazole rings. The reaction was then monitored by TLC.
In some cases, the reaction under reflux in THF gave the desired products in better yields (e.g.,
thiazoles 31 and 33). However, the oxidation of some 2-thiazolines at higher temperatures
gave complex mixtures that included the desired thiazoles. Even so, all of the 2-thiazolines
were converted to the corresponding 5-aminothiazoles in low to high yields. In particular,
with our synthetic methods, a range of unprecedented 5-N-arylamino-2-thiazolines and
–thiazoles with electron-donating and –withdrawing groups were provided. Additionally,
fluorescent emission by all of the 5-N-arylaminothiazoles was visually confirmed under
UV-lights.
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Table 2. Synthesis of 5-Aminothiazoles 25-43a
Ph
N
Ph
N
I2 (2 equiv)
S
S
Ph
Ph
Ph
Ph
THF, temp., time
N
N
Ph
Ph
4-24
25-43
Ph
Ph
Ph
N
N
N
N
S
S
N
S
Ph
Ph
Ph
Ph
Cl
N
N
25
26
27
Ph
Ph
Ph
reflux, 2 h, 75%b
reflux, 4 h, 96%b
reflux, 2 h, 48%b
Ph
N
S
Ph
Ph
Ph
N
Ph
N
S
N
S
N
Ph
Ph
30
N
Ph
N
Me
Ph
Ph
29
28
rt, 60 h, 62%b
rt, 39 h, 45%b
rt, 26 h, 45%b
Ph
Ph
Ph
N
S
N
S
N
S
Ph
Ph
Ph
Ph
Cl
Ph
N
N
N
32
31
33
MeO
reflux, 2 h, 54%b
MeO
Ph
reflux, 2 h, 43%b
rt, 43 h, 63%b
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Ph
Ph
Ph
Ph
N
N
N
S
N
N
S
N
S
N
Ph
Ph
Ph
N
Ph
34
35
36
Ph
Ph
9
rt, 23.5 h, 52%b
rt, 25 h, 61%b
rt, 25 h, 45%b
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11
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17
18
19
20
21
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23
24
25
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29
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31
32
33
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35
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N
N
N
S
N
S
Ph
Ph
Cl
N
37
38
Ph
Ph
rt, 48 h, 78%b
rt, 24 h, 24%b
Me
Me
N
N
S
S
N
Ph
Ph
Me
N
39
Me
40
Ph
Ph
rt, 22 h, 55%b
rt, 22 h, 58%b
NMe2
OMe
N
N
S
N
S
Ph
Ph
N
NMe2
OMe
42
41
Ph
Ph
rt, 23 h, 45%b
rt, 22 h, 86%b
NMe2
N
S
Ph
N
NMe2
43
Ph
rt, 21.5 h, 78%b
aThe reaction was carried out as follows, unless otherwise noted:
To a solution of thiazoline 4-24 (1.0 equiv) in THF was added
iodine, and the mixture was stirred. bIsolated yields.
Molecular Structures
The structures of thiazoles 17, 29, 32, 33, 35, and 42 were determined by X-ray analyses.
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Representative bond lengths and torsion angles are summarized in Table 3. Their molecular
structures are shown in Figure 1.
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R4
10
11
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13
14
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17
18
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11
11
1
S
7
7
N
1
7
1
N
10
N
10
5
4
5
4
5
4
N
R3
S
S
Ph
6 2
Bn
6 2
6 2
10
R1
N
3
N
8
N
3
8
3
8
thiazoles
R2
17, 29, 32 abd 42
Thiazole 33
9
Thiazole 35
Ph
9
9
Table 3. Dihedral angles and bond lengths of thiazoles 18, 29, 32, 33, 36, and 42.
Dihedral angles Bond lengths
S1-C2-C6-C7 N3-C4-C8-C9 S1-C5-N10-C11 C2-C6 C4-C8
Thiazole
S1-C2
C5-N10
R1, R2, R4 = H
R3 = Admanthyl
18
29
8.5(5)
10.3(5)
86.7(3)
1.469(5) 1.481(4) 1.408(4) 1.726(4)
R1, R3 = Ph
R2, R4 = H
13.6(3)
1.471(3) 1.485(3)
1.721(2)
1.413(3)
34.1(3)
92.3(2)
R1 = Cl
R2 = OMe
R3 = Ph
R4 = H
32
22.7(4)
33.0(3)
62.0(3)
1.470(3) 1.392(3) 1.726(3)
1.457(3)
Styryl
5.9(4)
1.475(4)
1.398(3) 1.737(3)
33
35
0.3(3)
49.0(3)
57.3(6)
1.446(4)
2-2Py
5-BnPh
1.472(7) 1.480(9) 1.398(7) 1.713(6)
1.6(8)
31.4(8)
R1, R2 = H
R3 = C6H4NMe2-4
R4 = NMe2
21.1(2)
21.4(2)
61.3(2)
1.471(2) 1.475(2) 1.394(2) 1.733(1)
42
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33
Figure 1. Molecular structures of (a) 17, (b) 29, (c) 32, (d) 33, (e) 35, and (f) 42. Ellipsoids are drawn at 50% probability.
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In all cases, amino groups at the 5-position are twisted from the thiazole rings. The torsion
angles at the 2-, 4- and 5-positions (i.e., S1-C2-C6-C7, N3-C4-C8-C9, and S1-C5-N10-C11)
were sensitive to the substituents at these positions, even if there appears to be almost no
inter- and intramolecular interactions between the substituents at the 2- and 5- positions.
The torsion angles of S1-C5-N10-C11 were affected by the substituents at the 2-position. In
particular, the introduction of a biphenyl group to the 2-position deviated the torsion angle of
S1-C5-N10-C11 to almost 90°, as in 29. In this case, the phenyl group at the 4-position also
deviated from the thiazole ring by more than 30°. The 2-methoxyphenyl group at the
4-position in 32 was deviated from the thiazolyl ring. It was oriented close to the
diphenylamino group, but did not influence the torsion angle of N3-C4-C8-C9 (33.0(3)°) in
32, which was nearly the same as that in 29 (34.1(3)°). In thiazole 33 with an
E-2-phenylethenyl group, the substituent at the 2-position was nearly in the same plane as that
of the thiazole ring. The deviation of a diphenylamino group at the 5-position in 33 was
slightly smaller than those in other thiazoles (49.0(3)°). The nitrogen atom in the pyridyl
group in 35 was located close to the sulfur atom, and the pyridine ring was nearly in the same
plane as that of the thiazole ring. Likewise, the deviation of the phenyl group on the
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nitrogen atom in 35 was slightly smaller than those in 17, 29, 32, and 42.
On the other
hand, the phenyl group at the 4-position in 35 (1.6(8)°) was deviated from the thiazole ring by
more than 30°. Finally, the introduction of Me2N groups on the phenyl ring attached to the
nitrogen atom at the 5-position also influenced the deviation of the substituents at the 2- and
4-positions, as shown in 42. These results of X-ray analyses of 5-aminothiazoles clearly
show that they adopt twisted structures in the ground state. Hence, the fluorescence shown
below does not follow a twisted intramolecular charge transfer mechanism, in which
fluorescent molecules with planar structures in the ground state twist to deviated structures in
excited states.15
Electronic Absorption and Fluorescence Spectroscopy
The photophysical properties of 5-aminothiazoles were examined. Table 4 shows their
UV-visible and fluorescence spectra in CHCl3 solutions. All of the compounds exhibited
strong absorption bands from 249 to 420 nm depending on the substituents. Generally,
electron-donating groups at the 5-positions and electron-withdrawing groups at the
2-positions shifted the absorptions and emissions to longer wavelengths. The longest
wavelengths of N,N-diphenylaminothiazoles 25–33 are in the range of 366–394 nm (entries
1–9). The replacement of an aromatic substituent at the 2-position with a 2- or 4-pyridyl
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group shifted the wavelengths from 367 nm to 388 and 394 nm, respectively (25 vs 27 and
28) (entries 1, 3, and 4). The introduction of chlorine or a phenyl group to the para-position
of the phenyl group at the 2-position slightly shifted the longest wavelengths to a longer
region by 4 and 11 nm (25 vs 26 and 29) (entries 1, 2, and 5). The methoxy group at the
ortho-position of the phenyl group at the 4-position also affected the wavelengths by ca. 12
nm (25 vs 31 and 26 vs 32) (entries 1, 7, 2, and 8). Notably, replacement of the phenyl
group on the nitrogen atom with an alkyl substituent showed a hypsochromic effect for the
longest wavelengths (entries 10–15). In particular, those of N-adamantyl thiazoles 17, 37,
and 38 were observed at 344 + 10 nm (entries 13–15). Thiazoles 39–43, which have
electron-donating groups such as methyl, methoxy, and dimethylamino groups at the
para-positions of the phenyl groups on the nitrogen atom, showed red shifts of the longest
wavelengths (entries 16–20), and those of 42 and 43 were observed at 412 and 420 nm,
respectively (entries 19 and 20).
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As in the UV-visible spectra, fluorescence spectra and their efficiencies could also be finely
tuned by the substituents at the 2-, 4-, and 5-positions. Replacement of an aromatic group at
the 4-position with a 2-phenylethenyl group quenched the efficiency of the emission, as
shown in 33 (entry 9). Likewise, the adamantyl group in 17, 37, and 38 highly decreased the
emission (entries 13–15). On the other hand, benzyl group in 34–36 did not have as strong
an influence as the adamantyl group (entries 10–12). The UV-visible spectra of 31 and 32
showed bathochromic shifts, but their fluorescence spectra were in regions almost identical to
those of 25 and 26, resulting in the observation of smaller Stokes shifts (entries 7 and 8).
Thiazoles 27 and 28, which have pyridyl groups at the 2-position showed emission with a
high efficiency at wavelengths longer than that of 25 (entries 3 and 4). Thiazoles 39, 40, and
41, which have methyl and methoxy groups at the para-position of the phenyl group on the
nitrogen atoms, also exhibited bathochromic shifts in fluorescence (entries 17 and 18).
Therefore, a change in emissions from light blue to deep yellow was achieved by changing
the substituents attached to the N,N-diarylaminothiazole cores (Figure 2). The emission
spectra of thiazoles 42 and 43, which have a dimethylamino group at the para-position,
showed excitation-wavelength-dependent luminescence15 (entries 19 and 20). For 42,
excitation at 310 nm resulted in lower-energy emission at 450 and 554 nm, whereas excitation
at 410 nm exhibited the emission at 616 nm (Figure 3). Although further elucidation is
necessary, the phenomena may be due to the multiple molecular conformations and/or several
singlet states with similar energy levels.
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Table 4. UV-vis and fluorescence spectra of thiazoles 25-43 in CHCl3
5
6
7
UV-vis
fluorescence
Stokes shift
(cm-1) [nm]
entry
Thiazole
ΦF
λabs (nm)
λem (nm)
log ε
8
9
NPh2
Ph
249
286
367
4.57
4.41
4.02
S
1
463
0.43
5650 [96]
5860 [103]
5026 [96]
Ph
25
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
NPh2
256
281
371
4.62
4.50
4.05
S
2
3
4
5
6
7
8
9
474
482
492
472
461
461
468
466
0.56
0.86
0.80
0.44
0.63
0.50
0.61
0.03
Cl
26
N
Ph
NPh2
N
S
289
328
388
4.33
3.99
4.00
N
Ph
27
NPh2
S
N
288
328
394
4.34
3.97
3.98
N
5056 [98]
5269 [94]
5335 [91]
4763 [83]
4674 [84]
5863 [100]
Ph
28
NPh2
S
N
310
332
378
4.39
4.18
4.02
Ph
29
Ph
NPh2
S
294
370
4.33
3.93
Ph
30
N
C6H4Me-2
NPh2
S
296
378
4.32
4.06
Ph
31
N
C6H4OMe-2
NPh2
S
296
384
4.38
4.16
Cl
N
C6H4OMe-2
NPh2
32
S
292
366
4.48
4.16
Ph
33
N
C2H2Ph
Bn
272
326
360
4.70
4.30
4.02
N
S
N
Ph
10
11
468
471
0.23
0.39
6410 [108]
5224 [93]
Ph
34
Ph
Bn
N
288
322
378
4.13
4.04
3.78
N
S
N
Ph
Ph
35
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Figure 2. Normalized fluorescence spectra of thiazoles 25-28 and 41 in CHCl3 (10-5 M);
excitation wavelength λex = 350 nm.
Figure 3. Absorbance and fluorescence spectra of thiazole 42 in CHCl3 (10-5 M). Absorbance
spectrum (blue dashed line) and fluorescence spectra under excitation at 310 nm (green solid
line) and 410 nm (red solid line).
The influence of the solvent on the photophysical properties of 5-aminothiazoles 26, 27, and
40 was elucidated. Nine solvents with different Reichardt polarity indices (ET(30))16 were
used, and the results are shown in Table 5. The thiazoles dissolved in all of the solvents with
low concentrations, except for glycerol. 1% Methanol in glycerol was then used as the most
polar solvent. The absorption spectra of 26, 27, and 40 were independent of the solvent
polarity except for those in 1% methanol in glycerol, in which the absorption was shifted to
longer wavelengths by about 5 to 12 nm. In contrast, solvent-dependent bathochromic shifts
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of more than 45 nm were observed for fluorescent spectra. Normalized spectra are shown in
Figure 4. As the solvents became more polar, the emissions became more red-shifted,
except that the emission of 40 in 1% methanol in glycerol was shifted to a shorter wavelength
by 6 nm compared with that in methanol. Notably, the relatively high emission was
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maintained even in polar solvents.17
The lifetimes of fluorescence was also
solvent-dependent. In all cases, the lifetimes in less polar solvents such as cyclohexane and
toluene were shorter than those in other solvents. These results suggest that the thiazoles are
less polar in the ground state and more polar in the excited state. Intramolecular charge
transfer may take place in the excited state.
Table 5. Solvatochromism of thiazoles 26, 27 and 40
solventa
glycerolb
57.0b
Et2O
CHCl3 CH2Cl2 CH3CN
C6H12
THF
MeOH
55.4
toluene
entry
Thiazole
Et (30) 30.9
33.9 34.5 37.4 39.1
40.7
45.6
371 374
370 371 372
466 478 477
371
480
371
489
370
493
380
λabs (nm)
454 466
499
λem (nm)
Ph
N
Stokes shift
(cm-1)
S
N
Ph
4928 5279 5568 6033 5917 6121
6504 6743
6276
Cl
1
c
0.33 0.52 0.50 0.61 0.62
1.07 1.11 1.13 1.23 1.37
2.41 3.46 3.77 4.47 4.60
0.65
1.04
4.93
0.52 0.48 0.62
1.46 1.16 1.05
5.02 5.16 5.06
Ph
ΦF
26
χ2 d
τ (ns)d
381 385
459 471
378 381 385
472 480 489
383
490
379
500
382
523
393
λabs (nm)
λem (nm)
526
Ph
Stokes shift
(cm-1)
N
N
S
N
4460 4743 5269 5413 5524 5701
6385 7057
6434
Ph
2
c
0.60 0.66 0.67 0.66 0.69
1.27 1.11 1.35 1.25 1.29
3.94 4.42 4.97 5.16 5.60
0.68
1.11
5.60
0.47 0.35 0.48
1.19 1.07 0.97
5.08 4.49 3.93
ΦF
Ph
χ2 d,e
27
τ (ns)d,e
382 386
467 480
380 382 383
481 492 495
383
499
382
511
380
516
387
λabs (nm)
λem (nm)
Me
510
Stokes shift
(cm-1)
4765 5073 5526 5853 5908 6070
6609 6936
6232
3
N
S
c
0.35 0.55 0.55 0.63 0.65
1.84 1.58 1.66 1.20 1.28
1.85 2.97 3.30 3.84 4.21
0.67
1.31
4.44
0.50 0.46 0.47
1.41 1.30 0.92
4.22 4.22 3.42
ΦF
Ph
N
χ2 d,e
Me
Ph
40
τ (ns)d,e
ac = 10-5 M. b1% of Methanol in glycerol. cExcited at maxmum absorption wavelength. dExcited at 365 nm.
eExcited at 405 nm.
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Figure 4. Normalized solvent-dependent fluorescence spectra of (a) 26, (b) 27 and (c) 40.
Recorded in cyclohexane, toluene, diethyl ether, THF, chloroform, dichloromethane,
acetonitrile, methanol and 1% MeOH in glycerol (10-5 M); excitation wavelength λex
=
corresponding longest-wavelength absorption maximum.
To further elucidate the solvent effects and to clarify the difference in polarity between the
ground and excited states, the Lippert-Mataga correlation18 was determined. Plots of the
Stokes shifts of the thiazoles 26, 27, and 40 versus the orientation polarization of the solvents
(Δf)19 are shown in Figure 5.
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Figure 5. Lippert-Mataga plot of (a) 26,
(b) 27 and (c) 40 in solvents of different polarity.
A linear correlation was observed, which indicated a solvent effect in the excited state,
although the standard deviation for 27 was greater than those of the other compounds. This
may be due to the hydrogen-bonding interaction between the nitrogen atom in 27 and the
hydrogen atom in MeOH. In fact, plots without MeOH clearly showed a better standard
deviation (Figure S1, see the Supporting Information). The change in dipolar moment
between the ground and excited states was further estimated on the basis of the plots, and the
results are shown in Table S1 (see the Supporting Information). Radiative and non-radiative
decay rate constants of thiazoles 26, 27 and 40 are also shown in Figure S2. A large change
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in the dipolar moment indicates a more pronounced intramolecular charge transfer for these
molecules in the excited state. For fluorescent molecules that show intramolecular charge
transfer, these are generally planar in the ground state and twisted in the excited state.20 On
the other hand, our 5-aminothiazoles highly deviate in the ground state as shown in X-ray
analyses. Therefore, they may be planarized21 to some extent in the excited statesto enable
more efficient delocalization of the electrons on the nitrogen atom to the thiazole rings and
the substituents at the 2-position.
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The photoluminescence properties of 5-aminothiazoles in the solid state were also
elucidated. The results for 26–28, 37, and 42 are shown in Table 6. Unlike the absorptions
and emissions in solution, general trends could not be determined, partly because of the
difficulty of obtaining reproducible data in the solid states. Nevertheless, photographs of
5-aminothiazoles show emission from blue to yellow in a solid state (Figure 6 and Figures S3
and S4 (see the Supporting Information)).
Table 6. UV-vis and fluorescence spectra of thiazoles 26, 27, 28, 37 and 42 as a solid state
Stokes Shift
b
λema (nm)
entry
Thiazole
S
λex (nm)
ΦF
(cm-1) [nm]
NPh2
Ph
1
347
453
0.14
6743 [106]
Cl
N
26
NPh2
N
S
2
3
395
410
466
0.15
0.07
3857 [71]
N
S
27
28
Ph
NPh2
464
576
7029 [166]
N
N
Ph
1-Adm
N
S
N
Ph
4
373
452
558
0.06
0.06
4685 [79]
Cl
Ph
37
N(C6H4NMe2-4)2
S
5
Ph
415
6175 [143]
N
42
Ph
aExcited at λex. bAbsolute fluorescent quantum yield.
Figure 6. Photograph showing the emission colors of 26−28, 37 and 42 when excited with a
UV lamp (365 nm).
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Electrochemical Properties.
5
6
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To determine the redox properties of 5-aminothiazoles, cyclic voltammetry measurements
were carried out in acetonitrile. In particular, the 5-aminothiazoles 26, 40–42 were chosen
as representative examples since they possess different electron-donating groups on the
aromatic rings at the 5-positions, and they were expected to be highly influential to
electrochemical oxidations. Representative cyclic voltammograms at a scan rate of 100
mV/s are shown in Figures 7 and 8, and the relevant data are listed in Table 7. The
5-aminothiazoles 26, 40, and 41 exhibited reversible one-electron oxidation below +0.7 V (vs
Fc/Fc+([n-Bu4N]ClO4/MeCN). Notably, the introduction of electron-donating groups such as
methyl and methoxy groups to the para-position of the phenyl rings on the nitrogen atom at
the 5-position reduced the oxidation potential by more than 0.1 V, from +0.635 V to +0.523 V
and +0.407 V.22 On the other hand, the cyclic voltammogram of 42 exhibited two reversible
oxidation processes at more negative potentials than those observed for 41. The first
oxidation wave can be attributed to the formation of a cation-radical species and the second is
ascribed to the successive oxidation of the cation-radical to its corresponding cation. This is
probably due to the introduction of more electron-donating dimethylamino groups to the
aromatic rings on the nitrogen atom at the 5-position, which may be able to accept two
electron oxidations. A similar two reversible oxidation processes has been observed for
4-aminophenyl diphenylamine.23
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Figure 7. Cyclic voltammograms of (a) 26,
(b) 40 and (c) 41. Recorded in acetonitrile;
0.1 M electrolyte [n-Bu4N][ClO4];
v = 100 mVs-1; Pt working electrode,
Ag/AgCl reference electrode and Pt counter electrode.
Figure 8. Cyclic voltammogram of 42.
Recorded in acetonitrile;
0.1 M electrolyte [n-Bu4N][ClO4];
v = 100 mVs-1; Pt working electrode,
Ag/AgCl reference electrode and Pt counter electrode.
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Table 7. Results of cyclic voltammetry and DFT calculations
HOMO-LUMO gap (eV)
HOMO (eV)
CVd DFTb
5
6
7
8
E1/2 (V)c
LUMOb (eV)
-2.00
entry
Thiazole
excited state
contribution
0.70
f
λabs (nm)
TD-DFTb
onseta
Ph
N
9
S
N
Ph
1
26
2.96
2.97
+0.635 -5.44 -5.51
HOMO-LUMO
418
0.23
10
11
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13
14
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40
41
42
43
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45
46
47
Cl
Ph
N(C6H4Me-4)2
S
N
2
3
4
40
41
42
2.87
2.88
2.84
2.84
2.81
2.55
+0.523 -5.32 -5.24
+0.407 -5.21 -5.06
-1.89
-1.71
HOMO-LUMO
HOMO-LUMO
HOMO-LUMO
0.70
0.70
0.70
436
441
486
0.32
0.20
0.20
Ph
Ph
N(C6H4OMe-4)2
S
N
Ph
Ph
Ph
N(C6H4NMe2-4)2
S
-0.058
-1.55
-0.78e
-5.01 -4.59
+0.209
N
Ph
aIn CHCl3, excited at 350 nm, c = 10-5 M. bThe first oxidation potential is shown. cDFT, TD-DFT (TD/ B3LYP/ 6-31+G (d, p)) calculations were carried out with
the use of optimized structures at B3LYP/ 6-31+G (d, p). Gas phase energies are shown. dEHOMO (eV) = -4.8-E1/2ox, based on ferrocene.ref. 25 eLUMO+1.
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Theoretical Calculations
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To gain further insight into the electronic structures of 5-aminothiazoles, DFT
calculations were performed for compounds 26, and 40–42 at the B3LYP/ 6-31+G (d,
p) level24 (Figure 9 and Table 7).
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LUMO+1
LUMO
HOMO
HOMO-1
Figure 9. Frontier orbitals (HOMO-1, HOMO, LUMO and LUMO+1) for 17 (left), 26
(middle) and 42 (right).
As shown in Figure 9, the HOMO of diphenylaminothiazoles 26 and 42 are localized on
the diphenylamino groups at the 5-position, whereas the LUMO of these compounds is
delocalized on both the thiazole ring and aromatic substituents at the 2 position. These
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orbital environments also support an intramolecular donor-acceptor–type π-electron
system where the substituents at the 5-position act as donors and both the thiazoles and
the substituents at the 2-position are acceptors. The longest wavelength calculated for
the 5-aminothiazole 26 is 418 nm with a large oscillator strength, which is red-shifted
compared to the experimental values (371 nm in CHCl3 in Table 4, and 347 nm in a
solid state in Table 7) (entry 1). Nevertheless, the calculated HOMO-LUMO gap for
26 (2.97 eV) is almost identical to that derived from the onset between absorption and
emission spectra. This similarity of the HOMO-LUMO gaps between calculated and
experimental values was also observed for 5-aminothiazoles 40–42 (entries 2–4).
Likewise, the tendency of a red-shift in the longest absorption wavelengths on going
from 26 to 40–42 is also reflected in the calculated results. In all cases, the main
contributions to these S0 to S1 electron transitions are from HOMO-LUMO (π-π*)
transitions.
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Thermal properties.
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To determine the thermal stability of 5-aminothiazoles, thermogravimetric and
differential thermal analyses of 26, 27 and 31 were carried out under a N2 atmosphere at
a heating rate of 5 K/min (Figure 10). These 5-aminothiazoles are thermally stable at
least below 280 °C, which is about 100 °C above their melting temperatures.
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Figure 10. TG-DTA curve of (a) 26, (b) 27
and (c) 31 at heating rate of 5 K min-1 under
N2 atmosphere.
Conclusion
In summary, we have described the synthesis, structures and photophysical properties of
a series of 5-N-arylaminothiazoles and have presented a theoretical elucidation of their
electronic structures. The reactions of thioamide dianions with thioformamides
followed by sequential oxidation with iodide gave 5-aminothiazoles via
5-amino-2-thiazolines.
They adopted highly varied structures due to subtle
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interactions between the substituents at the 2-, 4-, and 5-positions, as determined by
X-ray analyses. The longest wavelengths in their UV-visible spectra were within the
range from 360 to 420, whereas their emissions ranged from 460 to 610 nm. The
introduction of electron-donating groups to the aromatic groups attached to the nitrogen
atom at the 5-position shifted both the absorption and emission wavelengths, whereas
the substituents at the 4-position had almost no influence on these spectra. The
absorption spectra were not affected by the polarity of the solvent, whereas
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solvatochromism was observed for fluorescence spectra.
In this regard, the
relationship between solvent polarity and Stokes shifts was elucidated on the basis of
Lippert-Mataga plots. The change in the dipole moments of the 5-aminothiazoles
between the ground and excited states were evaluated, and the compounds were more
polarized in the latter state. Cyclic voltammograms exhibited reversible one-electron
oxidation curves except for 5-N, N-dimethylaminophenylthiazoles. Again, oxidation
potentials were controlled by the substituents at the 5-position. DFT calculations for
5-aminothiazoles showed that the HOMO is localized on the amino groups, whereas the
LUMO is delocalized on both the thiazole rings and the substituents at the 2-position.
Finally, TG/DTA showed that the 5-aminothiazoles are thermally stable below 280 °C.
These characteristic features and the ready availability of a variety of 5-aminothiazoles
suggest that they may be highly useful as fluorescent chemo- and biosensors. One of
the next steps in demonstrating the usefulness of these 5-aminothiazoles is to produce
those with a hydroxy group, which should enable the formation of inter- and
intramolecular hydrogen-bonding networks.
EXPERIMENTAL SECTION
1
13
General Remarks: The H and C NMR spectra were recorded in CDCl3. Chemical
shifts of protons are reported in δ values referenced to tetramethylsilane as an internal
standard in CDCl3, and the following abbreviations are used: s: singlet, d: doublet, t:
triplet, m: multiplet. All spectra were acquired in the proton-decoupled mode.
HRMS were recorded on a double-focusing mass spectrometer (EI). IR spectra were
obtained using KBr pellets or neat films. UV/vis absorption, fluorescence, and absolute
fluorescence quantum yields were obtained on the respective spectrometers.
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Electrochemical measurements were performed using a platinum working electrode, a
platinum wire counter electrode, and an Ag/Ag+ [0.01M AgCl] reference electrode in
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0.1
M
n-Bu4NClO4 (MeCN).
The potentials were calibrated with
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ferrocene/ferrocenium (Fc/Fc+). DMF was distilled from calcium hydride. All other
chemicals were used without further purification. Column chromatography was
performed on silica gel 60 N (spherical neutral) 100–210 µm. Flash column
chromatography was performed on silica gel 60 N (spherical neutral) 40–50 µm. All
manipulations were carried out under an argon atmosphere.
The compounds 1a,8
1b,8 1c,9 1g,26 1i,27 3a,8 3b,8 3c28 4–6,8 and 25–278 were prepared according to literature
procedures.
General Procedure for the Preparation of Thiazolines. To a solution of thioamide
(1 equiv) in THF was added slowly a 1.25 M solution of n- or s-butyllithium in
n-hexane (2 equiv) at 0 ℃, and the mixture was stirred for 10 min at this temperature.
To this was added thioformamide (1 equiv) at 0 ℃, and the mixture was stirred for
0−0.5 h at this temperature. To this was added iodine (2−3 equiv) at 0 ℃, and the
mixture was stirred for 2−3 h at 0 ℃ or room temperature. The resulting mixture was
poured into a saturated aqueous solution of Na2S2O3, and extracted with Et2O. The
organic layer was dried over MgSO4 and concentrated in vacuo. The residue was
purified by column chromatography (SiO2) to give the corresponding thiazolines.
General Procedure for the Preparation of Thiazoles. To a solution of thiazoline (1
equiv) in THF was added iodine (2 equiv) at room temperature, and the mixture was
stirred for 2−4 h under reflux or for 21.5−60 h at room temperature. The resulting
mixture was poured into a saturated aqueous solution of Na2S2O3, and extracted with
Et2O. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue
was purified by column chromatography (SiO2) to give the corresponding thiazoles.
N-[(2-Methylphenyl)methyl]benzenecarbothioamide (1f). To a solution of
benzaldehyde (0.21 mL, 2.0 mmol) in DMF (1.0 mL) was added elemental sulfur (0.07
g, 2.2 mmol) at room temperature. To this was added 2-methylbenzylamine (0.27 mL,
2.2 mmol) and the mixture was stirred for 2 h at 85 ℃. The mixture was cooled to
room temperature, 2-methylbenzylamine (0.24 mL, 2.0 mmol), elemental sulfur (0.06 g,
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2.0 mmol) and DMF (1.0 mL) were added, and the mixture was stirred for 1 h at 85℃.
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The combined organic phase was washed with a saturated aqueous solution of NaHCO3,
and extracted with Et2O. The organic layer was dried over MgSO4 and concentrated
under reduced pressure. The crude material was purified by column chromatography
(SiO2, hexane:EtOAc = 8:1) to give 1f (0.52 g, 99%) as a yellow solid (mp 88−92 ℃):
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1
IR (KBr) 3220, 2908, 1530, 1213, 944, 920, 748, 691 cm-1; H NMR (400 MHz,
CDCl3) δ 2.37 (s, 3H), 4.94 (d, J = 4.9 Hz, 2H), 7.19−7.27 (m, 3H, 7.28−7.37 (m, 3H),
7.44 (tt, J = 7.3 Hz, 1H), 7.55 (br, 1H), 7.71−7.73 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 19.1, 49.4, 126.4, 126.6, 128.46, 128.52, 129.4, 130.8, 131.1, 134.0, 137.0,
141.5, 198.8; MS (EI) m/z 241 (M+); HRMS (EI) Calcd for C15H15NS : 241.0925;
found : 241.0899.
N-(Phenylmethyl)-4-pyridinecarbothioamide (1d). According to the synthetic
procedure for 1f. The crude material was purified by column chromatography (SiO2,
hexane:EtOAc = 1:2) to give 1d (1.20 g, 90%) as a yellow solid (mp 136–137 °C): IR
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(KBr) 3187, 1594, 1559, 1436, 1401, 1347, 1063, 943, 829, 706, 696 cm-1; H NMR
(CDCl3) δ 4.97 (d, J = 4.9 Hz, 2H), 7.26−7.50 (m, 7H, Ar), 8.34−8.36 (m, 2H, Ar), 8.73
(br, 1H, NH); 13C NMR (CDCl3) δ 51.1, 120.8, 128.4, 128.5, 129.1, 135.7, 148.3, 149.8,
196.3; MS (EI) m/z 228 (M+); Elemental analysis calculated for C13H12N2S2: C,
68.39%; H, 5.30%; N, 1.27%. Found: C, 68.16%; H, 5.39%; N, 12.20%.
N-[(Phenylmethyl)-(1,1'-biphenyl)4-carbothioamide (1e). According to the synthetic
procedure for 1f. The crude material was purified by recrystallized from CH2Cl2/hexane
to give 1d (2.31 g, 95%) as a yellow solid (mp 191−192 ℃): IR (KBr) 3310, 3079,
3053, 3028, 2928, 1601, 1529, 1514, 1482, 1404, 1386, 1324, 1197, 1070, 933, 842,
1
768, 758, 742, 725, 694 cm-1; H NMR (400 MHz, CDCl3) δ 5.03 (d, J = 4.9 Hz, 2H),
7.42−7.45 (m, 8H), 7.58−7.62 (m, 4H), 7.75 (br, 1H), 7.84−7.86 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 51.2, 127.1, 127.2, 127.2, 128.0, 128.3, 128.4, 128.9, 129.0, 129.5,
139.9, 140.2, 144.1, 175.3; MS (EI) m/z 303 (M+); HRMS (EI) Calcd for C20H17NS :
303.1082; found : 303.1076.
N-[(2-Methylphenyl)methyl]-4-chlorobenzenecarbothioamide (1h). According to
the synthetic procedure for 1f. The crude material was purified by column
chromatography (SiO2, hexane:EtOAc = 8:1) to give 1h (0.33 g, 56%) as a yellow solid
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(mp 102−104 ℃): IR (KBr) 3218, 3001, 2836, 1603, 1436, 1536, 1486, 1086, 753, 723
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cm-1; 1H NMR (400 MHz, CDCl3) δ 3.88 (s, 3H), 5.00 (d, J = 5.4 Hz, 2H), 6.94−7.00 (q,
2H), 7.33−7.37 (m, 3H), 7.40 (dd, J = 1.5 Hz, 1.5 Hz, 1H), 7.78 (tt, J = 2.4 Hz, 2.2 Hz,
2H), 7.99 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 47.3, 55.5, 110.2, 120.9, 123.9,
128.0, 128.6, 129.8, 131.0, 137.1, 140.2, 157.6, 196.8; MS (EI) m/z 291 (M+); HRMS
(EI) Calcd for C15H14ClNOS : 291.0485; found : 291.0476.
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N-(1-Adamantyl)-N-phenylmethanethioamide
(3d).
To
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solution
of
N-(1-adamanthyl)-N-phenylmethaneamide (0.13 g, 0.5 mmol) in toluene (0.5 mL) were
added elemental sulfur (0.02 g, 0.55 mmol), DABCO (0.06 g, 0.55 mmol) and
trichlorosilane (0.06 mL, 0.55 mmol), and the mixture was stirred for 6 h at 115 ℃.
The combined organic phase was washed with a saturated aqueous sodium bicarbonate,
dried over MgSO4, and concentrated under reduced pressure. The crude material was
purified by column chromatography (SiO2, hexane:EtOAc = 8:1) to give 3d (0.09 g,
69%) as a white solid (mp 213−215 ℃): IR (KBr) 2905, 2850, 1592, 1492, 1452, 1384,
1359, 1344, 1272, 1195, 1075, 1004, 714, 697, 651 cm-1; 1H NMR (400 MHz, CDCl3) δ
1.64−1.69 (m, 6H), 1.96 (d, J = 2.4 Hz, 6H), 2.19 (s, 3H), 7.06−7.08 (m, 2H), 7.36−7.52
(m, 3H), 9.90 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 29.7, 35.5, 42.7, 62.9, 128.3,
129.1, 139.5, 188.3; MS (EI) m/z 271 (M+); HRMS (EI) Calcd for C17H21NS :
271.1395; found : 271.1403.
N,N-Bis(4-methylphenyl)methanethioamide (3e). According to the synthetic
procedure for 3d. The crude material was purified by column chromatography (SiO2,
hexane:EtOAc = 8:1) to give 3e (6.94 g, 94%) as a yellow solid (mp 114−115 ℃): IR
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(KBr) 3036, 2922, 1507, 1422, 1354, 1303, 1002, 915, 814, 587 cm-1; H NMR (400
MHz, CDCl3) δ 2.34 (s, 3H), 2.38 (s, 3H), 7.03−7.05 (m, 2H), 7.14−7.21 (m, 4H),
7.25−7.29 (m, 2H), 9.94 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 20.9, 21.2, 122.5,
127.3, 130.1, 130.3, 137.2, 138.3, 139.0, 143.6, 189.7; MS (EI) m/z 241 (M+); HRMS
(EI) Calcd for C15H15NS : 241.0925; found : 241.0918.
N,N-Bis(4-dimethylaminophenyl)methanethioamide (3f). According to the
synthetic procedure for 3d. The crude material was purified by column chromatography
(SiO2, hexane:EtOAc = 5:1) to give 3f (0.20 g, 67%) as a yellow solid (mp
171−172 ℃): IR (KBr) 2990, 2884, 2803, 1606, 1518, 1438, 1419, 1354, 1223, 1147,
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1122, 1013, 992, 818, 808, 580 cm-1; H NMR (400 MHz, CDCl3) δ 2.95 (s, 6H), 2.98
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(s, 6H), 6.62−6.66 (m, 2H), 6.71−6.75 (m, 2H), 7.01−7.06 (m, 2H), 7.16−7.20 (m, 2H),
9.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 40.3, 40.4, 112.2, 112.3, 123.7, 127.6,
130.6, 136.1, 149.3, 149.5, 188.0; MS (EI) m/z 299 (M+); HRMS (EI) Calcd for
C17H21N3S : 299.1456; found : 299.1447.
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(4R*,5S*)-4,5-Dihydro-2-(4-pyridyl)-N,N,4-triphenyl-5-thiazolamine
(7).
According to the general procedure for thiazolines, compound 7 was prepared. The
crude material was purified by column chromatography (SiO2, hexane:EtOAc:Et3N =
5:1:0.01) to give 7 (0.65 g, 80%) as an orange solid (mp 52−55 ℃): IR (KBr) 3054,
3026, 3005, 1591, 1548, 1491, 1448, 1410, 1266, 1236, 1213, 1032, 1002, 992, 963,
831, 753, 728, 694 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.97 (d, J = 3.4 Hz, 1H), 6.32 (d,
J = 3.4 Hz, 1H), 6.96 (d, J = 7.8 Hz, 4H), 7.00−7.05 (m, 2H), 7.18−7.29 (m, 9H), 7.58
(d, J = 5.9 Hz, 2H), 8.62 (d, J = 5.9 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 82.1, 82.6,
119.8, 121.6, 121.9, 123.4, 124.0, 126.2, 127.4, 128.1, 128.8, 129.3, 129.4, 139.2, 140.4,
145.4, 150.3, 166.8; MS (EI) m/z 407 (M+); HRMS (EI) Calcd for C26H21N3S :
407.1456; found : 407.1449.
(4R*,5S*)-2-[1,1’-Biphenyl]-4-yl-4,5-dihydro-N,N,4-triphenyl-5-thiazolamine (8).
According to the general procedure for thiazolines, compound 8 was prepared. The
crude material was purified by column chromatography (SiO2, hexane:EtOAc = 15:1) to
give 8 (0.87 g, 60%) as a brown liquid: IR (KBr) 3059, 3029, 2956, 2926, 1686, 1597,
1491, 1450, 1276, 1241, 1034, 948, 908, 846, 751, 728, 696 cm-1; 1H NMR (400 MHz,
CDCl3) δ 6.03 (d, J = 3.9 Hz, 1H), 6.32 (d, J = 3.9 Hz, 1H), 7.04−7.07 (m, 5H),
7.28−7.41 (m, 12H), 7.44−7.48 (m, 2H), 7.61−7.66 (m, 4H), 7.96 (d, J = 6.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 81.5, 82.4, 117.7, 121.4, 123.4, 123.8, 125.0, 126.1,
126.3, 127.1, 127.9, 128.8, 128.9, 129.4, 129.6, 140.0, 144.0, 145.6, 161.7; MS (EI) m/z
482 (M+); HRMS (EI) Calcd for C33H26N2S : 482.1817; found : 482.1811.
(4R*,5S*)-4,5-Dihydro-4-(2-methylphenyl)-N,N,2-triphenyl-5-thiazolamine
(9).
According to the general procedure for thiazolines, compound 9 was prepared. The
crude material was purified by column chromatography (SiO2, hexane:EtOAc:Et3N =
45:1:0.01) to give 9 (0.21 g, 50%) as a brown solid (mp 128−137 ℃): IR (KBr) 2923,
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