Noncatalytic electrophilic oxyalkylation of anilines with 2-trifluoroacetyl-1,3-benzothiazole

Article abstract of DOI:10.1055/s-0029-1218712

2-Trifluoroacetyl-1,3-benzothiazole reacts with anilines to form the corresponding trifluoromethyl-substituted alcohols. The reaction regioselectivity (ortho/para) was shown to depend strongly on the structure of the aniline. meta-Substituted anilines ten

Full text of DOI:10.1055/s-0029-1218712

PAPER
1633
Noncatalytic Electrophilic Oxyalkylation of Anilines with 2-Trifluoroacetyl-
1,3-benzothiazole
O
xyalkylation
a
of
A
nilines
v
w
ith2-Trifl
e
uoroacetyl-
l
1,3-benzothi
V
azole . Khodakovskiy,a,b Pavel K. Mykhailiuk,*a,b Dmitriy M. Volochnyuk,a Andrey A. Tolmacheva,b
a
Enamine Ltd., Alexandra Matrosova Street 23, Kiev 01103, Ukraine
Department of Chemistry, Kiev National Taras Shevchenko University, Volodymyrska Street 64, Kiev 01033, Ukraine
Fax +38(44)2351273; E-mail: Pashamk@gmx.de
b
Received 18 February 2010
HN
NH2
N
HN
Abstract: 2-Trifluoroacetyl-1,3-benzothiazole reacts with anilines
to form the corresponding trifluoromethyl-substituted alcohols. The
reaction regioselectivity (ortho/para) was shown to depend strong-
ly on the structure of the aniline. meta-Substituted anilines tend to
form the corresponding ortho-substituted products, in contrary to
the previous literature data.
OH
2
3
4
5
Me
Key words: anilines, Friedel–Crafts alkylation, ortho/para-substi-
tution, trifluoromethyl alcohols, 1,3-benzothiazole
NH2
HN
HN
NMe2
HN
The substitution of fluorine for hydrogen in organic com-
pounds is widely used to modify their biochemical char-
acteristics.1 Moreover, many market available
pharmaceuticals are fluorine-containing, although fluo-
rine scarcely occurs in organic matter.2 A trifluoromethyl
group, in particular, is one of the most attractive function-
al groups in organic chemistry, and thus incorporation of
this group into organic compounds is still of great inter-
est.3 Commercially available trifluoromethyl ketones –
hexafluoroacetone and trifluoropyruvate – are highly im-
portant building blocks commonly used to prepare CF3-
containing compounds.4 However, despite the great po-
tential of the both hexafluoroacetone and trifluoropyru-
vate,4 the chemistry of other trifluoroacetyl ketones had
received much less attention so far.5
6
7
8
9
10
NH2
NH2
NH2
NH2
N
11
12
13
14
Me
O
NH2
NEt2
NMe2
NH
O
OH
Me
15
16
17
18
Recently, we started a project aimed at the synthesis and
application of various trifluoroacetyl 1,3-azoles 1
(Figure 1).6 We have already studied the reaction of di-
verse electron rich heterocycles with 1 to provide the cor-
responding trifluoromethyl-substituted alcohols.6d–f An
addition of anilines to 1, however, received almost no at-
tention so far.6a Here, we have performed a systematic
study on the interaction of diverse anilines (compounds 2–
18, Figure 2) with 2-trifluoroacetyl-1,3-benzothiazole
(1a).
Figure 2 Substituted anilines 2–18
Among the variety of available representatives of 1,6a we
selected the highly active 2-trifluoroacetyl-1,3-benzothia-
zole (1a) (Figure 1) as the model compound to test the po-
tential of anilines 2–18 in the corresponding reaction of C-
oxyalkylation (Scheme 1).
NH2
NH2
R
1a, toluene
60–100 °C, 0.5–4 h
O
O
N
X
N
S
N
A1
A2
S
NH2
R
or
HO
F3C
F3C
25–99%
F3C
F3C
N
1
1a
HO
R
2–18
S
Figure 1 2-Trifluoroacetyl-1,3-azoles 1 and 2-trifluoroacetyl-1,3-
benzothiazole (1a)
2a–18a
Scheme 1 Synthesis of CF3-substituted alcohols 2a–18a from ani-
lines 2–18 and 2-trifluoroacetyl-1,3-benzothiazole (1a)
SYNTHESIS 2010, No. 10, pp 1633–1638
Advanced online publication: 24.03.2010
x
x.
x
x
.
2
0
1
0
DOI: 10.1055/s-0029-1218712; Art ID: Z04010SS
© Georg Thieme Verlag Stuttgart · New York

1634
P. V. Khodakovskiy et al.
PAPER
Table 1 CF3-Substituted Alcohols 2a–18a Prepared (continued)
2-Trifluoroacetyl-1,3-benzothiazole (1a) reacted indeed
with all anilines 2–18 under heating in toluene at 60–100
°C for 0.5–4 hours. The target trifluoromethyl alcohols
2a–18a were obtained in 25–99% yields (Table 1).
Ketone
Conditions
Product
Yield (%)
Me
HN
Table 1 CF3-Substituted Alcohols 2a–18a Prepared
7
toluene, 1a
100 °C, 1 h
99
HO
Ketone
Conditions
Product
Yield (%)
F3C
N
N
N
NH2
S
7a
2
toluene, 1a
100 °C, 2 h
HO
25
NMe2
F3C
N
S
8
toluene, 1a
100 °C, 1 h
HO
36
2a
F3C
HN
S
8a
3
toluene, 1a
100 °C, 1 h
HO
98
HN
F3C
N
S
9
toluene, 1a
100 °C, 1 h
HO
83
3a
F3C
N
S
9a
OH
N
4
5
6
toluene, 1a
60 °C, 0.5 h
HO
81
55
30
HN
F3C
S
10
toluene, 1a
100 °C, 1 h
HO
93
4a
F3C
N
S
N
N
S
10a
HN
toluene, 1a
100 °C, 1 h
F3C
HO
S
NH2
11
toluene, 1a
60 °C, 0.5 h
88
5a
F3C
NH2
HO
N
11a
toluene, 1a
100 °C, 4 h
HO
F3C
N
S
N
12
toluene, 1a
S
55
NH2
100 °C, 2 h
6a
F3C
HO
12a
Synthesis 2010, No. 10, 1633–1638 © Thieme Stuttgart · New York

PAPER
Oxyalkylation of Anilines with 2-Trifluoroacetyl-1,3-benzothiazole
1635
Table 1 CF3-Substituted Alcohols 2a–18a Prepared (continued)
Anilines 2–4 having the both ortho-positions blocked af-
forded the para-substituted products 2a–4a. On the con-
trary, aniline 5, with ortho/para-positions blocked gave
the only possible ortho-isomer 5a. However, although
anilines 6–18 could theoretically react at the both ortho-
and para-positions, all the products 6a–18a were obtained
as individual compounds and the formation of regioiso-
meric mixtures was not observed.
Ketone
Conditions
Product
Yield (%)
N
13
toluene, 1a
S
NH2
80
100 °C, 1 h
F3C
HO
The reactions of hexafluoroacetone and trifluoropyru-
vates with anilines are widely known and well described
in the literature.7 According to the literature reports, an in-
corporation of the appropriate fluorine-containing substit-
uents into aniline with the both ortho- and para-positions
free usually affords para-substituted products.7a–k We,
however, found that depending on the structure of the
aniline both the para- and ortho-substitutions can take
place. For example, anilines 6–10 reacted with 1a to form,
as expected, the products of para-substitution 6a–10a
(Table 1). The structures of the obtained compounds were
13a
N
14
toluene, 1a
100 °C, 3 h
S
63
NH2
F3C
HO
14a
NMe2
1
determined by H NMR and NOESY-experiments (see
Supporting Information). However, anilines 11–14 with
the both ortho/para-positions free rather unexpectedly
gave the products of ortho-substitution 11a–14a, in con-
trast to the previous literature data.7a–k We suggest, that
the regioselectivity of 11–14 in the reaction with 1a arises
from the presence of meta-substituents in 11–14, which
disfavors the substitution at the para-position, leading
thereby to the ortho-substituted products. Nevertheless,
compounds 15–18 with meta-substituents and the both
ortho/para positions free reacted with 1a to provide again
the products of para-substitution 15a–18a. Presumably,
the bulky N-alkyl groups in 15–17 protect the ortho-posi-
tions much more effectively than the meta-substituent
does with the para-position. The corresponding favorable
ortho-position is blocked in 18.
15
toluene, 1a
100 °C, 4 h
HO
48
F3C
N
S
15a
NH
16
toluene, 1a
100 °C, 1 h
HO
88
F3C
N
S
In summary, we have developed a very simple and effi-
cient one-step procedure to prepare CF3-substituted tertia-
ry alcohols from 2-trifluoroacetyl-1,3-benzothiazole and
anilines. The reaction regioselectivity (ortho/para) was
shown to depend strongly on the structure of the starting
aniline. meta-Substituted anilines with free nonhindered
ortho-positions tend to form ortho-substituted products
rather than para-substituted ones.
16a
NEt2
OH
N
17
toluene, 1a
60 °C, 0.5 h
HO
79
F3C
S
Ketone 1a was synthesized as reported previously.6a 1H, 13C and 19
F
17a
Me
O
NMR spectra were recorded on a Bruker Avance 500 spectrometer
at 499.9 MHz, 124.9 MHz, and 470.3 MHz, respectively. Chemical
shifts are reported in ppm downfield from TMS (1H, 13C) or CFCl3
(19F) as internal standards. Mass spectra were recorded on an Agi-
lent 1100 LCMSD SL instrument by chemical ionization (CI).
NH2
Me
O
N
HO
18
toluene, 1a
46
100 °C, 1 h
Oxyalkylation of Anilines 2–18 with 2-Trifluoroacetyl-1,3-ben-
zothiazole (1a); General Procedure
F3C
S
A mixture of 2-trifluoroacetyl-1,3-benzothiazole (1a; 231 mg, 1
mmol) and the appropriate aniline 2–18 (1 mmol) was stirred in tol-
uene (2 mL) under the conditions given in Table 1. The reaction
mixture was cooled to r.t., and the formed crystalline solid was col-
lected by filtration. The product was washed with CCl4 (1 mL) on
the filter and recrystallized from i-PrOH.
18a
Synthesis 2010, No. 10, 1633–1638 © Thieme Stuttgart · New York

1636
P. V. Khodakovskiy et al.
PAPER
2
1-(4-Amino-3,5-dimethylphenyl)-1-(1,3-benzothiazol-2-yl)-
2,2,2-trifluoroethanol (2a)
13C NMR (125 MHz, DMSO-d6): d = 78.38 (q, JC,F = 28.5 Hz),
1
113.53, 122.65, 123.26, 123.72, 124.94 (q, JC,F = 288.4 Hz),
Yield: 25%; mp 222–223 °C.
126.09, 126.78, 128.20, 135.02, 149.84, 153.27, 172.96.
19F NMR (470 MHz, DMSO-d6): d = –75.00.
APSI MS: m/z = 325 (M+ + 1).
1H NMR (500 MHz, DMSO-d6): d = 2.05 (6 H, s), 4.77 (2 H, s), 7.10
(2 H, s), 7.46 (1 H, dd, J = 6.5 Hz), 7.53 (1 H, dd, J = 6.5 Hz), 8.08
(3 H, m).
2
13C NMR (125 MHz, DMSO-d6): d = 18.60, 78.34 (q, JC,F = 28.9
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-[4-(methylami-
no)phenyl]ethanol (7a)
1
Hz), 120.35, 122.67, 123.27, 123.76, 124.99 (q, JC,F = 288.0 Hz),
126.09, 126.77, 126.78, 135.04, 145.54, 153.23, 173.03.
19F NMR (470 MHz, DMSO-d6): d = –75.88.
APSI MS: m/z = 353 (M+ + 1).
Yield: 99%; mp 120–121 °C.
1H NMR (500 MHz, DMSO-d6): d = 2.65 (3 H, d, J = 5.0 Hz), 5.87
(1 H, m), 6.53 (2 H, d, J = 8.5 Hz), 7.40 (2 H, d, J = 8.5 Hz), 7.48
(1 H, dd, J = 7.5, 6.5 Hz), 7.55 (1 H, dd, J = 8.0, 6.5 Hz), 8.09 (1 H,
d, J = 8.0 Hz), 8.12 (1 H, d, J = 7.5 Hz), 8.17 (1 H, s).
13C NMR (125 MHz, DMSO-d6): d = 29.98, 78.36 (q, 2JC,F = 28.9
Hz), 111.31, 122.70, 122.99, 123.74, 124.96 (q, JC,F = 288.0 Hz),
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-(8-methyl-1,2,3,4-
tetrahydroquinolin-6-yl)ethanol (3a)
Yield: 98%; mp 150–151 °C.
1
126.14, 126.82, 128.17, 135.01, 150.81, 153.26, 172.96.
19F NMR (470 MHz, DMSO-d6): d = –75.06.
APSI MS: m/z = 339 (M+ + 1).
1H NMR (500 MHz, DMSO-d6): d = 1.74 (2 H, m), 1.96 (3 H, s),
2.63 (2 H, m), 3.22 (2 H, m), 5.27 (1 H, br), 7.00 (1 H, s), 7.04 (1 H,
s), 7.46 (1 H, dd, J = 8.0, 7.5 Hz), 7.53 (1 H, dd, J = 8.0, 7.5 Hz),
8.02–8.18 (3 H, m).
13C NMR (125 MHz, DMSO-d6): d = 18.05, 21.71, 27.81, 41.81,
1-(1,3-Benzothiazol-2-yl)-1-[4-(dimethylamino)phenyl]-2,2,2-
trifluoroethanol (8a)
Yield: 36%; yellow oil.
78.35 (q, 2JC,F = 28.9 Hz), 119.22, 120.27, 122.35, 122.61, 123.70,
1
124.98 (q, JC,F = 288.0 Hz), 125.84, 126.01, 126.58, 126.70,
135.04, 144.14, 153.25, 173.06.
1H NMR (500 MHz, DMSO-d6): d = 2.89 (6 H, s), 6.72 (2 H, d,
J = 8.5 Hz), 7.44–7.52 (3 H, m), 7.56 (1 H, t, J = 7.5 Hz), 8.09 (1 H,
d, J = 8.5 Hz), 8.12 (1 H, d, J = 8.0 Hz), 8.26 (1 H, s).
19F NMR (470 MHz, DMSO-d6): d = –74.68.
APSI MS: m/z = 379 (M+ + 1).
13C NMR (125 MHz, DMSO-d6): d = 40.34, 78.27 (q, 2JC,F = 28.9
1
9-[1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-hydroxyethyl]-
2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol (4a)
Yield: 81%; mp 177–178 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.82 (4 H, m), 2.53 (4 H, m),
3.06 (4 H, m), 6.69 (1 H, s), 7.50 (1 H, dd, J = 8.0, 6.5 Hz), 7.56 (1
H, dd, J = 8.0, 6.5 Hz), 8.09 (1 H, d, J = 8.0 Hz), 8.13 (1 H, d,
J = 8.0), 9.00 (2 H, br).
Hz), 79.66, 111.98, 122.70, 123.73, 124.89 (q, JC,F = 287.5 Hz),
126.15, 126.84, 128.09, 134.98, 150.96, 153.24, 172.79.
19F NMR (470 MHz, DMSO-d6): d = –75.09.
APSI MS: m/z = 353 (M+ + 1) .
1-(1,3-Benzothiazol-2-yl)-1-(2,3-dihydro-1H-indol-5-yl)-2,2,2-
trifluoroethanol (9a)
Yield: 83%; mp 153–154 °C.
13C NMR (125 MHz, DMSO-d6): d = 21.45, 21.57, 22.15, 27.34,
2
49.01, 49.66, 79.79 (q, JC,F = 29.3 Hz), 108.40, 109.40, 112.66,
1H NMR (500 MHz, DMSO-d6): d = 2.89 (2 H, t, J = 8.5 Hz), 3.40
(2 H, t, J = 8.5 Hz), 5.72 (1 H, s), 6.46 (1 H, d, J = 8.0 Hz), 7.21 (1
H, d, J = 8.0 Hz), 7.31 (1 H, s), 7.48 (1 H, dd, J = 8.0, 7.0 Hz), 7.55
(1 H, dd, J = 8.5, 7.0 Hz), 8.09 (1 H, d, J = 8.5 Hz), 8.12 (1 H, d,
J = 8.0 Hz), 8.18 (1 H, s).
13C NMR (125 MHz, DMSO-d6): d = 29.47, 47.01, 78.55 (q,
2JC,F = 28.9 Hz), 107.57, 122.68, 123.24, 123.76, 124.56, 124.94 (q,
1JC,F = 288.0 Hz), 126.13, 126.71, 126.80, 129.08, 135.03, 153.23,
153.76, 173.04.
1
122.72, 123.75, 125.11 (q, JC,F = 288.0 Hz), 126.17, 126.22,
126.79, 135.33, 144.69, 152.08, 152.58, 172.60.
19F NMR (470 MHz, DMSO-d6): d = –74.73.
APSI MS: m/z = 421 (M+ + 1).
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-(6-methyl-1,2,3,4-
tetrahydroquinolin-8-yl)ethanol (5a)
Yield: 55%; mp 156–157 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.54–1.75 (2 H, m), 2.12 (3 H,
s), 2.65 (2 H, m), 2.96 (1 H, m), 3.14 (1 H, m), 5.40 (1 H, s), 6.78 (1
H, s), 6.89 (1 H, s), 7.48 (1 H, dd, J = 7.5 Hz), 7.53 (1 H, dd, J = 8.0,
7.5 Hz), 8.04 (1 H, d, J = 8.0 Hz), 8.12 (1 H, d, J = 7.5 Hz), 8.89 (1
H, s).
19F NMR (470 MHz, DMSO-d6): d = –74.91.
APSI MS: m/z = 351 (M+ + 1).
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-(1,2,3,4-tetrahydro-
quinolin-6-yl)ethanol (10a)
Yield: 93%; mp 101–102 °C.
13C NMR (125 MHz, DMSO-d6): d = 20.70, 21.47, 27.73, 41.64,
80.35 (q, 2JC,F = 28.5 Hz), 119.42, 122.69, 123.50, 123.58, 123.79,
1H NMR (500 MHz, DMSO-d6): d = 1.74 (2 H, m), 2.61 (2 H, m),
3.15 (2 H, m), 5.89 (1 H, s), 6.40 (1 H, d, J = 8.0 Hz), 7.08–7.19 (2
H, m), 7.46 (1 H, dd, J = 8.0, 7.5 Hz), 7.53 (1 H, dd, J = 8.0, 7.0 Hz),
8.03–8.15 (3 H, m).
13C NMR (125 MHz, DMSO-d6): d = 21.73, 27.43, 41.13, 78.40 (q,
2JC,F = 28.5 Hz), 112.92, 119.49, 122.51, 122.67, 123.73, 124.99 (q,
1JC,F = 288.0 Hz), 125.82, 126.08, 126.78, 127.92, 135.04, 146.44,
153.28, 173.05.
1
124.99 (q, JC,F = 288.0 Hz), 126.19, 126.36, 126.75, 131.36,
135.62, 142.36, 152.77, 171.61.
19F NMR (470 MHz, DMSO-d6): d = –72.87.
APSI MS: m/z = 379 (M+ + 1).
1-(4-Aminophenyl)-1-(1,3-benzothiazol-2-yl)-2,2,2-trifluoro-
ethanol (6a)
Yield: 30%; mp 163–164 °C.
19F NMR (470 MHz, DMSO-d6): d = –74.91.
APSI MS: m/z = 365 (M+ + 1).
1H NMR (500 MHz, DMSO-d6): d = 5.32 (2 H, br), 6.56 (2 H, d,
J = 8.0 Hz), 7.34 (2 H, d, J = 8.0 Hz), 7.46 (1 H, m), 7.53 (1 H, m),
8.09 (2 H, m), 8.15 (1 H, s).
Synthesis 2010, No. 10, 1633–1638 © Thieme Stuttgart · New York

PAPER
Oxyalkylation of Anilines with 2-Trifluoroacetyl-1,3-benzothiazole
1637
1-(2-Amino-4-pyrrolidin-1-ylphenyl)-1-(1,3-benzothiazol-2-yl)-
2,2,2-trifluoroethanol (11a)
Yield: 88%; mp 173–174 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.91 (4 H, m), 3.15 (4 H, m),
5.00 (2 H, s), 5.83 (1 H, s), 5.86 (1 H, d, J = 9.0 Hz), 6.98 (1 H, d,
J = 9.0 Hz), 7.47 (1 H, dd, J = 8.0, 7.5 Hz), 7.53 (1 H, dd, J = 7.5
Hz), 8.03 (1 H, d, J = 8.0 Hz), 8.10 (1 H, d, J = 7.5 Hz), 8.43 (1 H,
s).
1H NMR (500 MHz, DMSO-d6): d = 2.85 (6 H, s), 7.17 (1 H, d,
J = 8.0 Hz), 7.26 (1 H, dd, J = 8.0, 7.5 Hz), 7.39 (1 H, dd, J = 8.0,
7.5 Hz), 7.46 (2 H, m), 7.80 (1 H, d, J = 8.0 Hz), 7.90 (1 H, m), 8.14
(1 H, m), 8.18 (2 H, m), 8.57 (1 H, s).
13C NMR (125 MHz, DMSO-d6): d = 45.16, 80.39 (q, 2JC,F = 28.1
1
Hz), 112.91, 122.80, 123.78, 125.10, 125.11 (q, JC,F = 289.2 Hz),
125.13, 126.25, 126.28, 126.49, 126.75, 126.82, 126.88, 129.50,
132.54, 135.69, 152.53, 152.77, 172.31.
13C NMR (125 MHz, DMSO-d6): d = 25.40, 47.58, 80.06 (q,
2JC,F = 28.9 Hz), 100.13, 101.56, 108.04, 122.64, 123.71, 125.32 (q,
1JC,F = 288.8 Hz), 126.11, 126.68, 128.98, 135.72, 148.43, 149.16,
152.73, 172.71.
19F NMR (470 MHz, DMSO-d6): d = –73.31.
APSI MS: m/z = 394 (M+ + 1).
19F NMR (470 MHz, DMSO-d6): d = –72.17.
APSI MS: m/z = 403 (M+ + 1).
1-(1,3-Benzothiazol-2-yl)-1-[4-(ethylamino)-1-naphthyl]-2,2,2-
trifluoroethanol (16a)
Yield: 88%; mp 186–187 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.30 (3 H, t, J = 7.0 Hz), 3.29
(3 H, q, J = 7.0 Hz), 6.43 (1 H, br s), 6.54 (1 H, d, J = 8.5 Hz), 7.20
(1 H, dd, J = 8.0, 7.0 Hz), 7.28 (1 H, dd, J = 8.0, 7.0 Hz), 7.45 (2 H,
m), 7.66 (1 H, d, J = 8.0 Hz), 7.90 (1 H, d, J = 8.0 Hz), 8.08 (1 H, d,
J = 8.5 Hz), 8.11 (1 H, d, J = 7.0 Hz), 8.18 (1 H, d, J = 8.0 Hz), 8.32
(1 H, s).
1-(4-Amino-2,3-dimethylphenyl)-1-(1,3-benzothiazol-2-yl)-
2,2,2-trifluoroethanol (12a)
Yield: 55%; mp 147–148 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.92 (3 H, s), 2.17 (3 H, s), 4.95
(2 H, br s), 6.50 (1 H, d, J = 8.5 Hz), 7.02 (1 H, d, J = 8.5 Hz), 7.47
(1 H, dd, J = 8.0, 7.0 Hz), 7.52 (1 H, dd, J = 8.5, 7.0 Hz), 8.02 (1 H,
d, J = 8.5 Hz), 8.11 (1 H, d, J = 8.0 Hz), 8.94 (1 H, br s).
13C NMR (125 MHz, DMSO-d6): d = 13.56, 20.75, 80.33 (q,
2JC,F = 28.1 Hz), 118.10, 118.61, 122.69, 123.13, 123.80, 125.10 (q,
1JC,F = 289.2 Hz), 125.14, 126.23, 126.78, 135.65, 137.84, 145.18,
152.75, 171.87.
13C NMR (125 MHz, DMSO-d6): d = 14.45, 38.06, 80.48 (q,
2JC,F = 28.1 Hz), 101.32, 119.25, 122.69, 122.69, 123.71, 123.90,
1
124.41, 125.31 (q, JC,F = 288.0 Hz), 126.04, 126.10, 126.52,
126.62, 127.71, 132.34, 135.85, 145.96, 152.81, 173.08.
19F NMR (470 MHz, DMSO-d6): d = –72.05.
APSI MS: m/z = 403 (M+ + 1).
19F NMR (470 MHz, DMSO-d6): d = –72.97.
APSI MS: m/z = 353 (M+ + 1) .
2-[1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoro-1-hydroxyethyl]-5-
(diethylamino)phenol (17a)
Yield: 79%; mp 202–203 °C (dec.).
1-(1-Amino-5,6,7,8-tetrahydronaphthalen-2-yl)-1-(1,3-benzo-
thiazol-2-yl)-2,2,2-trifluoroethanol (13a)
Yield: 80%; mp 171–172 °C.
1H NMR (500 MHz, DMSO-d6): d = 1.63 (2 H, m), 1.73 (2 H, m),
2.30 (2 H, m), 2.62 (2 H, m), 4.96 (2 H, br), 6.40 (1 H, d, J = 8.0
Hz), 7.03 (1 H, d, J = 8.0 Hz), 7.47 (1 H, dd, J = 8.0, 7.0 Hz), 7.52
(1 H, dd, J = 8.0, 7.0 Hz), 8.04 (1 H, d, J = 8.0 Hz), 8.11 (1 H, d,
J = 8.0 Hz), 8.84 (1 H, br).
1H NMR (500 MHz, DMSO-d6): d = 1.05 (6 H, t, J = 6.8 Hz), 3.25
(4 H, q, J = 6.8 Hz), 6.06 (1 H, d, J = 1.2 Hz), 6.16 (1 H, dd, J = 9.2,
1.2 Hz), 7.23 (1 H, d, J = 9.2 Hz), 7.45 (1 H, dd, J = 7.5 Hz), 7.51
(1 H, dd, J = 7.5 Hz), 7.97 (1 H, s), 8.02 (1 H, d, J = 7.5 Hz), 8.08
(1 H, d, J = 7.5), 9.81 (1 H, s).
13C NMR (125 MHz, DMSO-d6): d = 12.96, 44.14, 78.80 (q,
2JC,F = 30.2 Hz), 99.30, 103.18, 108.41, 122.56, 123.62, 125.20 (q,
1JC,F = 288.0 Hz), 125.91, 126.53, 129.83, 135.47, 149.56, 152.92,
157.09, 173.14.
13C NMR (125 MHz, DMSO-d6): d = 22.58, 23.13, 24.42, 29.91,
80.37 (q, 2JC,F = 28.5 Hz), 116.90, 117.36, 122.68, 123.52, 123.81,
1
125.04, 125.16 (q, JC,F = 288.0 Hz), 126.23, 126.78, 135.65,
19F NMR (470 MHz, DMSO-d6): d = –75.72.
APSI MS: m/z = 397 (M+ + 1).
138.67, 145.16, 152.75, 171.92.
19F NMR (470 MHz, DMSO-d6): d = –73.07.
APSI MS: m/z = 379 (M+ + 1).
1-(4-Amino-2,5-dimethoxyphenyl)-1-(1,3-benzothiazol-2-yl)-
2,2,2-trifluoroethanol (18a)
Yield: 46%; mp 135–136 °C.
1-(1-Amino-2-naphthyl)-1-(1,3-benzothiazol-2-yl)-2,2,2-trifluo-
roethanol (14a)
Yield: 63%; mp 195–196 °C.
1H NMR (500 MHz, DMSO-d6): d = 6.07 (2 H, br s), 7.14 (1 H, d,
J = 9.0 Hz), 7.35 (1 H, d, J = 9.0 Hz), 7.41 (1 H, dd, J = 8.0, 7.0 Hz),
7.48 (2 H, m), 7.54 (1 H, dd, J = 8.0, 7.0 Hz), 7.75 (1 H, d, J = 8.0
Hz), 8.06 (1 H, d, J = 8.0 Hz), 8.12 (2 H, m), 8.98 (1 H, s).
1H NMR (500 MHz, DMSO-d6): d = 3.24 (3 H, s), 3.71 (3 H, s), 5.09
(2 H, s), 6.32 (1 H, s), 7.08 (1 H, s), 7.43 (1 H, dd, J = 8.0, 7.0 Hz),
7.49 (1 H, dd, J = 8.0, 7.0 Hz), 7.69 (1 H, s), 7.99 (1 H, d, J = 8.0
Hz), 8.06 (1 H, d, J = 8.0 Hz).
13C NMR (125 MHz, DMSO-d6): d = 56.43, 56.56, 77.64 (q,
2JC,F = 28.9 Hz), 110.04, 111.70, 111.87, 122.45, 123.46, 125.12 (q,
1JC,F = 288.8 Hz), 125.76, 126.38, 135.49, 140.06, 140.87, 152.73,
153.13, 173.53.
2
13C NMR (125 MHz, DMSO-d6): d = 80.80 (q, JC,F = 28.5 Hz),
112.73, 115.71, 122.74, 122.94, 123.92, 124.49, 125.16, 125.43 (q,
1JC,F = 289.2 Hz), 125.89, 126.40, 126.90, 127.30, 128.14, 134.42,
135.68, 144.35, 152.65, 172.02.
19F NMR (470 MHz, DMSO-d6): d = –73.51.
APSI MS: m/z = 385 (M+ + 1).
19F NMR (470 MHz, DMSO-d6): d = –73.34.
APSI MS: m/z = 375 (M+ + 1).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
1-(1,3-Benzothiazol-2-yl)-1-[4-(dimethylamino)-1-naphthyl]-
2,2,2-trifluoroethanol (15a)
Yield: 48%; mp 155–156 °C.
Synthesis 2010, No. 10, 1633–1638 © Thieme Stuttgart · New York

1638
P. V. Khodakovskiy et al.
PAPER
(6) (a) Khodakovskiy, P. V.; Volochnyuk, D. M.; Panov, D. M.;
Pervak, I. I.; Zarudnitskii, E. V.; Shishkin, O. V.;
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Synthesis 2010, No. 10, 1633–1638 © Thieme Stuttgart · New York