2-(Trifluoroacetyl)imidazoles, 2-trifluoroacetyl-1,3-thiazoles, and 2-trifluoroacetyl-1,3-oxazoles

Article abstract of DOI:10.1055/s-2008-1032197

A facile method of trifluoroacylation of imidazoles, 1,3-thiazoles, and 1,3-oxazoles with trifluoroacetic anhydride resulted in a set of heterocyclic trifluoromethyl-containing ketones. Unlike common ketones, these compounds form stable hydrates and enter into noncatalytic ene reactions with terminal olefins affording the corresponding allyl alcohols. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032197

948
PAPER
2-(Trifluoroacetyl)imidazoles, 2-Trifluoroacetyl-1,3-thiazoles,
and 2-Trifluoroacetyl-1,3-oxazoles
2
-(Trifluoroac
a
e
tyl)imidaz
v
oles, -1,3-th
e
l
-
1,3-oxazole
V
s
. Khodakovskiy,a,b Dmitriy M. Volochnyuk,*a,c Dmitriy M. Panov,a,b Igor I. Pervak,c
Evgenij V. Zarudnitskii,c Oleg V. Shishkin,d Aleksandr A. Yurchenko,c Alexander Shivanyuk,a,b
Andrey A. Tolmacheva,b
a
Enamine Ltd., 23 A. Matrosova st., 01103 Kiev, Ukraine
Fax +380(44)5373253; E-mail: D.Volochnyuk@enamine.net
National Taras Shevchenko University, 62 Volodymyrska st., 01033 Kiev-33, Ukraine
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, 02094 Kiev-94, Ukraine
Institute for Scintillation Materials, National Academy of Science of Ukraine, 60 Lenina ave., 61001 Kharkiv, Ukraine
b
c
d
Received 15 November 2007; revised 11 December 2007
Dedicated to Prof. A. M. Pinchuk on the occasion of his 70th birthday
dizes alcohols in noncatalytic Meerwein–Ponndorf reac-
tions.9
Abstract: A facile method of trifluoroacylation of imidazoles, 1,3-
thiazoles, and 1,3-oxazoles with trifluoroacetic anhydride resulted
in a set of heterocyclic trifluoromethyl-containing ketones. Unlike
common ketones, these compounds form stable hydrates and enter
into noncatalytic ene reactions with terminal olefins affording the
corresponding allyl alcohols.
The reactivity of more complicated trifluoromethyl ke-
tones bearing electron-acceptor heterocyclic fragments at
the carbonyl group has not been studied systematically.
Although a few hetaryl trifluoromethyl ketones have been
obtained, their chemical properties have remained virtual-
ly unexplored.10 The 2-, 3-, and 4-(trifluoroacetyl)py-
ridines form stable gem-diols;10d this indicates their high
electrophilicity and potential applicability for the synthe-
sis of various trifluoromethyl-containing compounds.
Key words: fluorine compounds, acylations, ketones, nitrogen-
containing heterocycles, stable hydrates
Highly reactive trifluoromethyl ketones1 such as hexa-
fluoroacetone and trifluoropyruvates have been widely
employed as electrophilic reagents for the modification of
various biologically active compounds with trifluoro-
methyl groups.2 Due to the influence of two strong elec-
tron-withdrawing groups, the chemical reactivity of these
compounds differs from that of common ketones. For ex-
ample, they show extremely high activity in the reactions
with various nucleophiles and form stable hydrates,2b,3
semiketals,2b,4 and semiaminals5 upon the addition of wa-
ter, alcohols, and aliphatic amines, respectively. Their hy-
drolytically unstable Schiff bases rearrange into C-
oxyalkylation products on heating;6 and undergo ene7 and
Baylis–Hillman reactions.8 Hexafluoroacetone also oxi-
We report here on facile methods for the synthesis of var-
ious hetaryl trifluoromethyl ketones and on an exploration
of their chemical properties.
Regel–Büchel acylation,10a phosphorylation, and
silylation11 of imidazoles, 1,3-thiazoles, and 1,3-oxazoles
with acid chlorides (Et3N, apolar solvent) occur at the
meso-position to give the corresponding acylated deriva-
tives in preparative yields. In the present study we utilize
this synthetic approach for the acylation of imidazoles,
1,3-thiazoles, and 1,3-oxazoles 1 with trifluoroacetic an-
hydride, to prepare 2-(trifluoroacetyl)imidazoles, -1,3-thi-
azoles, and -1,3-oxazoles 4 (Scheme 1). The acylation of
COCF3
COCF3
A
N
A
N
A
N
A
N
TFAA
Et3N
acyl transfer
CF3
B
B
–
B
B
toluene
X
X
X
X
O
1
2
3
4
A
A
N
N
CF3
TFAA
MeCN
B
B
X
X
OH
5f: A=B = C6H4, X = NMe
5g: A = CH, B = N, X = NMe
5h: A = CMe, B = CH, X = S
5i: A=B = C6H4, X = S
For A, B, X, see Table 1
Scheme 1
SYNTHESIS 2008, No. 6, pp 0948–0956
x
x
.
x
x
.2
0
0
8
Advanced online publication: 28.02.2008
DOI: 10.1055/s-2008-1032197; Art ID: P13307SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
2-(Trifluoroacetyl)imidazoles, -1,3-thiazoles, and -1,3-oxazoles
949
azoles 1 occurs according to a postulated mechanism10a,12
via the intermediate heterocyclic ylide 3 (Scheme 1).
Table 1 Structures and Yields of Hetaryl Trifluoromethyl Ketones 4
Entry
Starting material 1 Product 4
Yielda (%)
The least electron-accepting imidazoles 1a–d and 1f were
acylated at –19 °C (Et3N, toluene) to give the correspond-
ing trifluoromethyl ketones 4a–d,f in 75–89% yield
(Scheme 1, Table 1, entries 1–4, 6). The addition of tri-
fluoroacetic acid anhydride to 1a–d and 1f resulted in the
precipitation of salts 2, which dissolved upon the addition
of triethylamine (Scheme 1).
N
N
CF3
1
8210a
N
N
Me
Me
O
1a
1b
4a
4b
N
N
CF3
N
N
N
N
2
3
75
85
O
The acylation of compounds 1f and 1i in acetonitrile gave
ketones 4f and 4i as well as 2,2,2-trifluoro-1,1-bis(hetar-
yl)ethanols 5f and 5i (Scheme 1). The latter compounds
appear to be formed by the reactions of intermediates 3f
and 3i with the corresponding ketones 4. It seems likely
that the high polarity of acetonitrile facilitates this reac-
tion through the stabilization of bipolar ylides 3. The
yields of compounds 5 can be increased to up to 78% by
reversal of the order of addition of trifluoroacetic anhy-
dride and triethylamine.
N
N
CF3
O
1c
4c
N
N
CF3
4
5
6
7
77
83
89
65
N
N
The acylation of imidazo[1,5-a]pyridine (1m) is compli-
cated by acylation at position 1 affording 1-(trifluoro-
acetyl)imidazo[1,5-a]pyridine (4m¢) (Scheme 2).12a
However, the yield of the target product 4m was increased
to 75% if the reaction was carried out at –19 °C.
Bu
Bu
O
N
1d
4d
N
CF3
Cl
Cl
N
N
Me
Me
O
1e
4e
F3COC
N
N
CF3
O
N
N
N
N
TFAA, Et3N
+
COCF3
N
N
N
N
Me
Me
75%
4m
25%
1f
4f
1m
4m'
N
N
CF3
N
N
Scheme 2
N
N
Me
Me
O
1g
4g
The acylation of tetrazole gave an inseparable mixture of
unidentified products, most probably because of the extru-
sion of nitrogen from the intermediate ylide. This is con-
firmed by evolution of gas after the addition of
triethylamine to the reaction mixture.
N
N
CF3
8
72
S
S
O
1h
1i
4h
4i
The acylation of oxadiazoles also failed (Scheme 3),
probably because of the electron deficiency at the nitrogen
atom, which hampers the N-acylation with trifluoroacetic
anhydride, which is a first step of the acylation at position
2. This problem could be circumvented by the use of less
electron-deficient and more reactive trimethylsilyl deriv-
ative 611e as starting material (Scheme 3).
CF3
O
N
S
N
9
10
11
12
99
S
N
N
CF3
80
Ph
O
Ph
O
O
Ketones 4 react with water to form stable hydrates 7
(Scheme 4). According to 19F NMR spectroscopic studies
of samples of hydrates 7 in aqueous solutions and wet or-
ganic solvents, the stability of the hydrates strongly de-
pends on the electron-withdrawing ability of the
heterocyclic unit. In the case of the least electrophilic im-
idazole derivatives 4a–d (Table 1, entries 1–4), the hydra-
tion degree was found to be 35–40%, whereas 4e and 4f
(Table 1, entries 5 and 6) are hydrated by 65% and 75%,
respectively. Highly electrophilic ketones 4g–l,n are com-
pletely hydrated in aqueous solutions.
1j
4j
CF3
O
N
O
N
O
6510b
1k
4k
N
N
N
N
CF3
56
Ph
S
Ph
S
O
1l
4l
a Yields refer to isolated and purified product 4.
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

950
P. V. Khodakovskiy et al.
PAPER
N
N
TFAA,
Et3N, toluene
1. 6, KF, DB-18-C-6,
toluene, 110 °C
N
N
N
N
CF3
HO
N
N
Ph
Ph
O
Ph
O
O
Ph
O
2. MeOH, H2O, F–
O
F3C
4n
5n
1n
TMSBr
Py
N
N
TFAA
pentane, –30 °C
Ph
TMS
O
6
Scheme 3
Compounds 4 react with aliphatic amines to give stable strongly magnetically shielded, and this results in an up-
gem-amino alcohols, e.g. 9 (Scheme 4), whereas the reac- field shift of their NMR signals into the range between
tions with anilines afford unstable products, some of d = –83.7 and –81.9 ppm.
which rearrange into C-alkylated compounds, e.g. 11, un-
der heating (Scheme 4). At 156 °C the most electrophilic
ketone 4i underwent an ene reaction with allylbenzene
(12) to give compound 13 in 64% yield.
The structures of representative compounds 4m, 5g, and
7i were confirmed by single-crystal X-ray analysis
(Figures 1– 3). In the crystalline state, molecules 5g form
infinite chains stabilized by intermolecular hydrogen
The compositions and structures of all the compounds ob- bonds between hydroxy groups and nitrogen atoms of the
tained were unambiguously established by mass spec- triazole fragments (Figure 2). Hydroxy groups of mole-
trometry, elemental analysis, and NMR and IR cules 7i in the crystalline state form intermolecular hydro-
spectroscopy. The 19F NMR spectra of ketones 4 contain gen bonds to the nitrogen atoms of the benzothiazole
singlets between d = –75.2 and –71.2 ppm. The fluorine rings, resulting in infinite hydrogen-bonded tapes
atoms of hydrates 7 and alcohols 5 are, as expected, more (Figure 3).
A
N
H2O
CF3
OH
B
4
X
HO
7e–l,n
N
H
N
NH2
S
4i or 7i
+
HO
CF3
9
8
NH2
NH2
heat
N
+
4i or 7i
S
HO CF3
11
10
heat
+
4i or 7i
N
CF3
OH
S
12
13
Scheme 4
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

PAPER
2-(Trifluoroacetyl)imidazoles, -1,3-thiazoles, and -1,3-oxazoles
951
synthesis of heterocyclic trifluoromethyl-containing ke-
tones. The chemical properties of the ketones bearing im-
idazole and benzimidazole fragments are similar to those
of phenyl and methyl trifluoromethyl ketones, whereas
the other ketones can be considered as analogues of tri-
fluoropyruvate and hexafluoroacetone. The compounds
form stable hydrates and aminals and, unlike common ke-
tones, undergo noncatalytic ene reactions with terminal
olefins, affording the corresponding allyl alcohols.
All commercially available azoles were purchased from Aldrich
(1a, 1d, 1f, 1k), Avocado (1h), Fluka (1b, 1c), Hangzhou Pharma
& Chem (1e), and Merck (1i), and were distilled prior to use. Com-
pounds 1g,13 1j,14 1l,15 1n,16 and 1p17 were prepared by literature
procedures. Et3N was distilled from Phth2O and KOH, and toluene
and MeCN were distilled from P2O5. 1H, 13C, and 19F NMR spectra
of samples in CDCl3 or DMSO-d6 were recorded at r.t. on a Bruker
Avance DRX 500 instrument. Mass spectra were recorded on an
MX-1321 spectrometer (EI, 70 eV). Satisfactory microanalyses
were obtained for all new substances: C, 0.33; H, 0.45; N, 0.25.
Figure 1 Molecular structure of compound 4n
2,2,2-Trifluoro-1-hetarylethanones 4 by Trifluoroacylation of
Azoles 1; General Procedure
TFAA (2.52 g, 0.012 mol) was added dropwise (20 min) to a stirred
soln of azole 1 (0.01 mol) in toluene (100 mL) at –19 °C. The addi-
tion of TFAA was generally accompanied with the precipitation of
2, which readily dissolved on slow addition of Et3N (1.21 g, 0.012
mol). After stirring for 6–8 h, the resulting yellow soln was slowly
warmed to r.t. and left overnight. Removal of the solvent in vacuo,
and treatment of the resulting oil with H2O (sonication) gave hy-
drates 7, which were converted into ketones 4 by distillation
(Method A) or sublimation (Method B) under reduced pressure.
Figure 2 (a) Molecular and (b) crystal structures of compound 5g
2,2,2-Trifluoro-1-(1-methyl-1H-imidazol-2-yl)ethanone (4a)
Method A: 88–92 °C (12 Torr); white crystals; yield: 82%; mp 56
°C.
IR (film): 3383, 3138, 3117, 3032, 1705, 1482, 1416, 1300, 1280,
1196, 1160, 948, 905, 798, 743, 675 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.07 (s, 3 H), 7.23 (s, 1 H), 7.37
(s, 1 H).
13C NMR (125 MHz, CDCl3): d = 36.3, 116.3 (q, 1JCF = 290.0 Hz),
129.3, 132.0, 138.0, 170.7 (q, 2JCF = 36.5 Hz).
19F NMR (470 MHz, CDCl3): d = –73.65.
MS (EI, 70 eV): m/z (%) = 178 (20) [M]+, 109 (100) [M – CF3]+, 81
(7) [M – COCF3]+, 78 (13), 69 (25) [CF3]+, 54 (40), 52 (15), 42 (25),
40 (17), 32 (33).
2,2,2-Trifluoro-1-(1-vinyl-1H-imidazol-2-yl)ethanone (4b)
Method A: 114–115 °C (12 Torr); white crystals; yield: 75%; mp 54
°C.
IR (film): 3384 (br), 3137, 1672, 1647, 1464, 1413, 1279, 1205,
1171, 1092, 1063, 943, 903, 744 cm–1.
1H NMR (500 MHz, CDCl3): d = 5.22 (dd, J = 8.7, 1.7 Hz, 1 H),
5.47 (dd, J = 15.6, 1.7 Hz, 1 H), 7.41 (s, 1 H), 7.59 (s, 1 H), 7.81 (dd,
J = 15.6, 8.7 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 107.7, 116.2 (q, 1JCF = 290.0 Hz),
Figure 3 (a) Molecular and (b) crystal structures of compound 7i
123.4, 130.0, 132.7, 136.8, 170.9 (q, 2JCF = 36.9 Hz).
19F NMR (470 MHz, CDCl3): d = –73.72.
MS (EI, 70 eV): m/z (%) = 190 (76) [M]+, 121 (100) [M – CF3]+, 95
(12), 94 (95) [M – COCF3 + H]+, 79 (68), 69 (67) [CF3]+, 67 (25),
66 (15), 45 (57), 43 (20), 41 (59), 40 (42), 39 (31).
In conclusion, the reactions of imidazoles, 1,3-thiazoles,
and 1,3-oxazoles with trifluoroacetic anhydride in the
presence of triethylamine provide a facile method for the
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

952
P. V. Khodakovskiy et al.
PAPER
1-(1-Allyl-1H-imidazol-2-yl)-2,2,2-trifluoroethanone (4c)
Method A: 123–125 °C (12 Torr); white liquid; yield: 85%.
2,2,2-Trifluoro-1-(1-methyl-1H-1,2,4-triazol-5-yl)ethanone (4g)
Method A: 54–55 °C (12 Torr); colorless liquid; yield: 64%.
IR (film): 3381 (br), 3115, 2993 1701, 1647, 1467, 1414, 1311,
1275, 1228, 1203, 1161, 1074, 993, 955, 943, 904, 791, 737 cm–1.
IR (film): 3448, 3130, 3026, 2966, 1740, 1492, 1475, 1416, 1371,
1300, 1286, 1205, 1171, 980, 928, 891, 783, 744, 715, 681 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.98 (d, J = 5.5 Hz, 2 H), 5.07 (d,
J = 17 Hz, 1 H), 5.22 (d, J = 10 Hz, 1 H), 5.86–5.96 (m, 1 H), 7.28
(s, 1 H), 7.32 (s, 1 H).
1H NMR (500 MHz, CDCl3): d = 4.26 (s, 3 H), 8.08 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 39.1, 115.6 (q, 1JCF = 289.7 Hz),
144.1, 151.4, 171.4 (q, 2JCF = 39.2 Hz).
13C NMR (125 MHz, CDCl3): d = 50.9, 116.4 (q, 1JCF = 290.5 Hz),
19F NMR (470 MHz, CDCl3): d = –75.21.
MS (EI, 70 eV): m/z (%) = 180 (9) [M + H]+, 142 (31), 110 (100)
[M – CF3]+, 83 (29) [M – COCF3 + H]+, 69 (20), 56 (26), 55 (11),
43 (17), 32 (30), 31 (17).
119.1, 128.2, 131.6, 132.2, 137.5, 170.4 (q, 2JCF = 36.5 Hz).
19F NMR (470 MHz, CDCl3): d = –73.62.
MS (EI, 70 eV): m/z (%) = 204 (14) [M]+, 135 (38) [M – CF3]+, 107
(30), 41 (100), 39 (28).
2,2,2-Trifluoro-1-(4-methyl-1,3-thiazol-2-yl)ethanone (4h)
Method A: 110–114 °C (12 Torr); yellow liquid; yield: 72%.
1-(1-Butyl-1H-imidazol-2-yl)-2,2,2-trifluoroethanone (4d)
Method A: 160–162 °C (12 Torr); white crystals; yield: 77%;
mp 32–33 °C.
IR (film): 3113, 2983, 2933, 1712, 1499, 1432, 1338, 1209, 1192,
1164, 972, 881, 772, 725, 584 cm–1.
IR (film): 3113 3101, 2965, 2860, 1699, 1475, 1412, 1275, 1223,
1204, 1161, 952, 904, 727, 669 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.95 (t, J = 7.3 Hz, 3 H), 1.35 (m,
2 H), 1.77 (m, 2 H), 4.41 (t, J = 7.5 Hz, 2 H), 7.27 (s, 1 H), 7.37 (s,
1 H).
1H NMR (500 MHz, CDCl3): d = 2.59 (s, 3 H), 7.47 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 17.2, 116.1 (q, 1JCF = 289.7 Hz),
124.5, 157.6, 158.4, 173.2 (q, 2JCF = 37.2 Hz).
19F NMR (470 MHz, CDCl3): d = –74.09.
MS (EI, 70 eV): m/z (%) = 195 (23) [M]+, 126 (100) [M – CF3]+, 98
(12) [M – COCF3]+, 72 (8), 71 (46), 69 (25) [CF3]+, 45 (44), 39 (48),
32 (66), 31 (24).
13C NMR (125 MHz, CDCl3): d = 13.4, 19.5, 32.8, 48.9, 116.4 (q,
1JCF = 290.0 Hz), 128.4, 132.1, 137.5, 170.4 (q, 2JCF = 36.2 Hz).
19F NMR (470 MHz, CDCl3): d = –71.26.
MS (EI, 70 eV): m/z (%) = 220 (23) [M]+, 191 (15) [M – C2H5]+,
178 (33) [M – C3H6]+, 151 (65) [M – CF3]+, 123 (78) [M – COCF3]+,
95 (100) [M – CF3 – C4H8]+, 81 (25) [M – C3H6 – COCF3]+, 69 (46)
[CF3]+, 57 (45), 56 (12), 41 (100), 40 (14).
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoroethanone (4i)
Method B: 130–150 °C (0.5 Torr); yellow crystals; yield: 99%;
mp 117–118 °C.
IR (film): 3064, 3031, 1716, 1478, 1340, 1212, 1161, 1125, 895,
725 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.58–7.67 (m, 2 H), 8.01 (d,
J = 8.4 Hz, 1 H), 8.30 (d, J = 7.2 Hz, 1 H).
1-(5-Chloro-1-methyl-1H-imidazol-2-yl)-2,2,2-trifluoro-
ethanone (4e)
Method A: 107–108 °C (12 Torr); white crystals; yield: 83%;
13C NMR (125 MHz, CDCl3): d = 116.0 (q, 1JCF = 290.3 Hz), 122.3,
mp 68–69 °C.
126.7, 127.9, 129.3, 137.3, 153.7, 158.7, 175.1 (q, 2JCF = 37.9 Hz).
IR (film): 3386 (br) 3120, 1701, 1475, 1415, 1394, 1286, 1196,
1163, 1103, 976, 899, 852, 744, 707 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.98 (s, 3 H), 7.30 (s, 1 H).
19F NMR (470 MHz, CDCl3): d = –73.91.
MS (EI, 70 eV): m/z (%) = 231 (56) [M]+, 162 (100) [M – CF3]+,
134 (75) [M – COCF3]+, 90 (16), 78 (12), 69 (32) [CF3]+, 63 (16).
13C NMR (125 MHz, CDCl3): d = 33.1, 116.3 (q, 1JCF = 290.5 Hz),
128.2, 129.5, 137.5, 170.0 (q, 2JCF = 36.5 Hz).
2,2,2-Trifluoro-1-(5-phenyl-1,3-oxazol-2-yl)ethanone (4j)
Method B: 130–140 °C (0.5 Torr); white crystals; yield: 80%;
mp 76–77 °C.
19F NMR (470 MHz, CDCl3): d = –74.21.
MS (EI, 70 eV): m/z (%) = 214 (8) [M + 2]+, 212 (33) [M]+, 145 (26)
[M + 2 – CF3]+, 143 (100) [M – CF3]+, 80 (34), 69 (11) [CF3]+, 42
(13).
IR (film): 3500–2900 (br), 1712, 1554, 1475, 1452, 1388, 1274,
1205, 1172, 1130, 1080, 999, 945, 916, 767, 746, 692 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.46–7.57 (m, 3 H), 7.72 (s, 1 H),
2,2,2-Trifluoro-1-(1-methyl-1H-benzimidazol-2-yl)ethanone
(4f)
Method B: 130–150 °C (0.5 Torr); white crystals; yield: 89%;
mp 107–108 °C.
7.78–787 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 115.9 (q, 1JCF = 288.8 Hz), 125.6,
125.7, 125.9, 129.4, 131.1, 152.6, 156.6, 167.1 (q, 2JCF = 39.4 Hz).
19F NMR (470 MHz, CDCl3): d = –74.24.
IR (film): 3048, 2954, 2913, 2848, 1723, 1458, 1218, 1173, 1156,
960, 748, 735 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.14 (s, 3 H), 7.41 (dd, J = 8.5, 7.0
Hz, 1 H), 7.46 (d, J = 8.5 Hz, 1 H), 7.52 (dd, J = 8.5, 7.0 Hz, 1 H),
7.97 (d, J = 8.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 32.2, 110.6, 116.2 (q,
1JCF = 290.1 Hz), 123.1, 124.8, 127.9, 136.9, 140.7, 142.4, 173.8 (q,
2JCF = 36.5 Hz).
19F NMR (470 MHz, CDCl3): d = –73.37.
MS (EI, 70 eV): m/z (%) = 241 (100) [M]+, 172 (74) [M – CF3]+,
116 (47), 105 (40), 89 (10), 77 (54), 69 (16) [CF3]+, 51 (16).
1-(1,3-Benzoxazol-2-yl)-2,2,2-trifluoroethanone (4k)
Method B: 130–140 °C (0.5 Torr); white crystals; yield: 65%;
mp 93–94 °C.
IR (film): 3093, 3023, 1732, 1527, 1376, 1206, 1175, 1161, 1082,
981, 920, 737, 688 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.53 (t, J = 7.7 Hz, 1 H), 7.64 (t,
J = 7.7 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 229 (12) [M + H]+, 228 (100) [M]+, 160
(10), 159 (75) [M – CF3]+, 131 (21) [M – COCF3]+, 104 (17), 77
(33), 51 (13).
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

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2-(Trifluoroacetyl)imidazoles, -1,3-thiazoles, and -1,3-oxazoles
953
13C NMR (125 MHz, CDCl3): d = 112.1, 115.6 (q, 1JCF = 289.7 Hz),
123.4, 126.8, 130.5, 140.5, 150.8, 152.5, 169.7 (q, 2JCF = 39.9 Hz).
collected by filtration, washed with aq EtOH and recrystallized
from i-PrOH.
19F NMR (470 MHz, CDCl3): d = –74.95.
MS (EI, 70 eV): m/z (%) = 215 (26) [M]+, 146 (100) [M – CF3]+,
119 (31), 102 (41), 91 (13), 90 (24), 78 (26), 69 (46) [CF3]+, 64 (50),
63 (36), 39 (21), 38 (13), 32 (25), 31 (28).
2,2,2-Trifluoro-1,1-bis(1-methyl-1H-benzimidazol-2-yl)eth-
anol (5f)
White crystals; yield: 78%; mp 195–196 °C.
1H NMR (500 MHz, DMSO-d6): d = 3.71 (s, 6 H), 7.27 (dd, J = 8.0,
7.2 Hz, 2 H), 7.35 (dd, J = 8.0, 7.2 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2
H), 7.68 (d, J = 8.0 Hz, 2 H), 8.74 (s, 1 H).
13C NMR (125 MHz, DMSO-d6): d = 32.0, 76.6 (q, 2JCF = 30.2 Hz),
111.0, 120.2, 122.7, 123.9, 124.6 (q, 1JCF = 288.0 Hz), 136.9, 141.5,
148.2.
19F NMR (470 MHz, DMSO-d6): d = –74.02.
MS (EI, 70 eV): m/z (%) = 361 (11), 360 (83) [M]+, 359 (38), 292
(12), 291 (69) [M – CF3]+, 263 (24), 229 (24), 159 (56), 146 (100),
145 (13), 133 (25), 132 (100), 131 (89), 104 (21), 90 (10), 77 (34).
2,2,2-Trifluoro-1-(5-phenyl-1,3,4-thiadiazol-2-yl)ethanone (4l)
Method B: 140–150 °C (0.5 Torr); yellow crystals; yield: 56%;
mp 108–109 °C.
IR (film): 3450–2850 (br), 1727, 1461, 1425, 1340, 1238, 1188,
1161, 1053, 898, 769, 692 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.51–7.65 (m, 3 H), 8.07 (d,
J = 7.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 115.7 (q, 1JCF = 289.7 Hz), 128.2,
128.8, 129.6, 133.1, 161.1, 173.5 (q, 2JCF = 39.8 Hz), 174.5.
19F NMR (470 MHz, CDCl3): d = –73.70.
MS (EI, 70 eV): m/z (%) = 258 (79) [M]+, 189 (40) [M – CF3]+, 162
(15), 161 (34) [M – COCF3]+, 121 (13), 104 (20), 103 (100), 77 (37),
76 (12), 69 (36) [CF3]+, 51 (17).
2,2,2-Trifluoro-1,1-bis(1-methyl-1H-1,2,4-triazol-5-yl)ethanol
(5g)
White crystals; yield: 18%; mp 166–168 °C (sublimed).
1H NMR (500 MHz, DMSO-d6): d = 3.77 (s, 6 H), 8.00 (s, 2 H), 8.97
(s, 1 H).
13C NMR (125 MHz, DMSO-d6): d = 37.8, 73.6 (q, 2JCF = 31.3 Hz),
124.0 (q, JCF = 288.0 Hz), 149.4, 150.2.
19F NMR (470 MHz, DMSO-d6): d = –76.80.
2,2,2-Trifluoro-1-(imidazo[1,5-a]pyridin-3-yl)ethanone (4n)
Extracted from crude product with benzene; yellow crystals; yield:
75%; mp 142–143 °C.
IR (film): 3442 (br), 3072, 1641, 1461, 1371, 1362, 1263, 1207,
1176, 1146, 1124, 1093, 889, 763, 652 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.48 (dd, J = 6.8 Hz, 1 H), 7.65
(dd, J = 8.8, 6.8 Hz, 1 H), 8.05 (s, 1 H), 8.15 (d, J = 8.8 Hz, 1 H),
9.52 (d, J = 6.8 Hz, 1 H).
2,2,2-Trifluoro-1,1-bis(4-methyl-1,3-thiazol-2-yl)ethanol (5h)
Brown crystals; yield: 6%; mp 141–142 °C.
1H NMR (500 MHz, DMSO-d6): d = 2.38 (s, 6 H), 7.41 (s, 2 H), 8.77
(s, 1 H).
13C NMR (125 MHz, CDCl3): d = 117.0 (q, 1JCF = 289.3 Hz), 118.2,
13C NMR (125 MHz, DMSO-d6): d = 17.3, 77.7 (q, 2JCF = 30.2 Hz),
118.5, 126.9, 127.1, 127.2, 130.5, 136.4, 168.1 (q, 2JCF = 36.2 Hz).
117.7, 123.7 (q, 1JCF = 289.2 Hz), 152.9, 165.9.
19F NMR (470 MHz, CDCl3): d = –72.73.
19F NMR (470 MHz, DMSO-d6): d = –75.75.
MS (EI, 70 eV): m/z (%) = 294 (16) [M]+, 225 (74) [M – CF3]+, 196
MS (EI, 70 eV): m/z (%) = 214 (81) [M]+, 145 (100) [M – CF3]+,
117 (64) [M – COCF3]+, 90 (39), 69 (11) [CF3]+, 63 (22).
(21), 126 (100), 99 (25), 72 (12), 71 (32), 45 (32), 39 (21).
2,2,2-Trifluoro-1-(5-phenyl-1,3,4-oxadiazol-2-yl)ethanone (4p)
A soln of 6 (4.807 g, 22.02 mmol) in hexane (20 mL) was added
dropwise to a stirred soln of TFAA (9.250 g, 6.22 mL, 44.04 mmol)
in hexane (20 mL) at –30 °C. The reaction mixture was allowed to
warm to r.t. and was stirred for 12 h. The precipitate that formed was
collected by filtration and washed with hexane; this gave compound
4p.
1,1-Bis(1,3-benzothiazol-2-yl)-2,2,2-trifluoroethanol (5i)
White crystals; yield: 67%; mp 138–139 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.42–7.58 (m, 4 H), 8.02–8.12
(m, 4 H), 9.12 (s, 1 H).
2
13C NMR (125 MHz, DMSO-d6): d = 78.2 (q, JCF = 29.5 Hz),
122.6, 123.2 (q, 1JCF = 288.7 Hz), 123.6, 126.3, 126.8, 135.0, 152.3,
Yield: 3.430 g (64%); mp 128–130 °C.
167.4.
IR (film): 3500–3000 (br), 1739, 1605, 1542, 1520, 1480, 1453,
1415, 1332, 1308, 1288, 1244, 1222, 1175, 1083, 1042, 1006, 938,
799, 745, 718, 695, 654, 627, 525, 476 cm–1.
1H NMR (500 MHz, benzene-d6): d = 6.92–7.06 (m, 3 H), 7.76 (d,
J = 7.0 Hz, 2 H).
19F NMR (470 MHz, DMSO-d6): d = –74.10.
MS (EI, 70 eV): m/z (%) = 366 (67) [M]+, 297 (80) [M – CF3]+, 269
(26), 232 (44), 162 (100), 135 (60), 134 (69), 108 (26), 69 (21)
[CF3]+, 32 (13).
Hydrates 7; General Procedure
1
13C NMR (125 MHz, benzene-d6): d = 115.9 (q, JCF = 289.0 Hz),
A soln of the appropriate ketone 4 in benzene in an open vial was
placed in a cold water bath and left overnight. The precipitate was
collected by filtration, washed with benzene, and dried in the open
air. The yields were almost quantitative.
122.5, 128.2, 129.3, 133.3, 157.5, 167.0, 167.3 (q, 2JCF = 31.2 Hz).
19F NMR (470 MHz, benzene-d6): d = –74.8.
MS (EI, 70 eV): m/z (%) = 242 (31) [M]+, 146 (11), 145 (81), 105
(8), 103 (32), 89 (5), 78 (6), 77 (100), 76 (11), 69 (21) [CF3]+, 63
(11), 59 (6), 51 (19), 50 (12), 39 (9), 31 (39), 30 (51).
1-(5-Chloro-1-methyl-1H-imidazol-2-yl)-2,2,2-trifluoroethane-
1,1-diol (7e)
White crystals; mp 100–120 °C (sublimed).
1H NMR (500 MHz, DMSO-d6): d = 3.69 (s, 3 H), 7.02 (s, 1 H), 7.96
(br s, 2 H).
2,2,2-Trifluoro-1,1-bis(hetaryl)ethanols 5; General Procedure
TFAA (0.01 mol) was added dropwise to a stirred soln of the appro-
priate azole 1 (0.01 mol) and Et3N (0.01 mol) in MeCN (20 mL) at
0 °C. The reaction mixture was warmed to r.t., then stirred for 3 h,
and subsequently treated with H2O (20 mL). The precipitate was
13C NMR (125 MHz, DMSO-d6): d = 32.5, 90.8 (q, 2JCF = 32.7 Hz),
120.6, 123.1 (q, 1JCF = 289.2 Hz), 123.5, 142.6.
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

954
P. V. Khodakovskiy et al.
PAPER
19F NMR (470 MHz, CDCl3): d = –83.42.
MS (EI, 70 eV): m/z (%) = 230 (95) [M]+, 212 (17) [M – H2O]+, 161
(17) [M – CF3]+, 143 (100) [M – CF3 – H2O]+, 80 (25), 74 (10), 69
(13) [CF3]+, 42 (17).
1H NMR (500 MHz, DMSO-d6): d = 7.40 (t, J = 7.5 Hz, 1 H), 7.49
(dd, J = 7.5 Hz, 2 H), 7.75 (d, J = 7.5 Hz, 2 H), 7.77 (s, 1 H), 8.38
(br s, 2 H).
13C NMR (125 MHz, DMSO-d6): d = 90.2 (q, 2JCF = 33.5 Hz), 122.9
1
(q, JCF = 289.2 Hz), 123.1, 124.7, 127.5, 129.5, 129.6, 152.1,
2,2,2-Trifluoro-1-(1-methyl-1H-benzimidazol-2-yl)ethane-1,1-
159.0.
diol (7f)
White crystals; mp 129–137 °C.
1H NMR (500 MHz, DMSO-d6): d = 3.97 (s, 3 H), 7.26 (dd, J = 7.5
Hz, 1 H), 7.34 (dd, J = 7.5 Hz, 1 H), 7.60 (d, J = 7.5 Hz, 1 H), 7.70
(d, J = 7.5 Hz, 1 H), 8.21 (br s, 2 H).
19F NMR (470 MHz, DMSO-d6): d = –82.99.
MS (EI, 70 eV): m/z (%) = 259 (3) [M]+, 242 (16), 241 (100) [M –
H2O]+, 172 (92) [M – H2O – CF3]+, 116 (87), 105 (70), 89 (25), 77
(91), 69 (31) [CF3]+, 63 (12), 51 (33), 50 (15), 39 (15).
13C NMR (125 MHz, DMSO-d6): d = 32.2, 91.4 (q, 2JCF = 33.5 Hz),
111.1, 119.8, 122.3 (q, 1JCF = 289.0 Hz), 123.1, 124.3, 136.8, 140.3,
149.0.
19F NMR (470 MHz, DMSO-d6): d = –81.97.
1-(1,3-Benzoxazol-2-yl)-2,2,2-trifluoroethane-1,1-diol (7k)
White crystals; mp 110–115 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.36–7.46 (m, 2 H), 7.68–7.72
(d, 1 H), 7.76–7.80 (d, 1 H), 8.24 (s, 2 H).
2
MS (EI, 70 eV): m/z (%) = 246 (0.4) [M]+, 229 (13), 228 (100) [M
– H2O]+, 177 (0.5) [M – CF3]+, 159 (96) [M – H2O – CF3]+, 132 (11),
131 (16), 104 (17), 77 (32), 69 (42) [CF3]+, 51 (24), 50 (10), 45 (50).
13C NMR (125 MHz, DMSO-d6): d = 90.1 (q, JCF = 33.2 Hz),
111.4, 120.6, 122.3 (q, JCF = 289.0 Hz), 125.1, 126.4, 139.9, 150.1,
161.0.
19F NMR (470 MHz, DMSO-d6): d = –82.51.
MS (EI, 70 eV): m/z (%) = 233 (20) [M]+, 215 (50) [M – H2O]+, 164
(17) [M – CF3]+, 146 (100) [M – H2O – CF3]+, 119 (67), 102 (31),
92 (10), 91 (47), 90 (27), 69 (42) [CF3]+, 64 (68), 63 (50), 39 (21)
2,2,2-Trifluoro-1-(1-methyl-1H-1,2,4-triazol-5-yl)ethane-1,1-
diol (7g)
White crystals; mp 122–128 °C.
1H NMR (500 MHz, DMSO-d6): d = 3.98 (s, 3 H), 7.94 (s, 1 H), 8.31
(br s, 2 H).
2,2,2-Trifluoro-1-(5-phenyl-1,3,4-thiadiazol-2-yl)ethane-1,1-
diol (7l)
White crystals; mp 111–116 °C.
13C NMR (125 MHz, DMSO-d6): d = 37.9, 90.4 (q, 2JCF = 33.2 Hz),
122.8 (q, 1JCF = 289.3 Hz), 149.5, 151.1.
19F NMR (470 MHz, DMSO-d6): d = –82.68.
MS (EI, 70 eV): m/z (%) = 179 (5) [M – H2O]+, 128 (37) [M –
CF3]+, 110 (100) [M – CF3 – H2O]+, 83 (13), 69 (12) [CF3]+, 56 (15),
43 (12).
1H NMR (500 MHz, DMSO-d6): d = 7.50–7.60 (m, 3 H), 8.00 (d,
J = 6.5 Hz, 2 H), 8.78 (br s, 1 H).
13C NMR (125 MHz, DMSO-d6): d = 91.8 (q, 2JCF = 33.5 Hz), 122.9
(q, 1JCF = 289.2 Hz), 128.2, 129.7, 130.0, 132.1, 169.6, 170.5.
19F NMR (470 MHz, DMSO-d6): d = –83.65.
2,2,2-Trifluoro-1-(4-methyl-1,3-thiazol-2-yl)ethane-1,1-diol
(7h)
White crystals; mp 98–102 °C.
1H NMR (500 MHz, DMSO-d6): d = 2.43 (s, 3 H), 7.16 (s, 1 H), 7.90
(s, 2 H).
MS (EI, 70 eV): m/z (%) = 276 (3) [M]+, 258 (68) [M – H2O]+, 207
(4) [M – CF3]+, 189 (52) [M – H2O – CF3]+, 161 (46) [M – H2O –
COCF3]+, 121 (16), 103 (100), 77 (35), 76 (15), 69 (41) [CF3]+, 63
(11), 51 (23), 50 (14).
13C NMR (125 MHz, DMSO-d6): d = 17.0, 91.7 (q, 2JCF = 32.2 Hz),
2,2,2-Trifluoro-1-(5-phenyl-1,3,4-oxadiazol-2-yl)ethane-1,1-
diol (7p)
116.9, 122.8 (q, 1JCF = 289.3 Hz), 152.7, 167.2.
White crystals; mp 114 °C (dec).
1H NMR (500 MHz, DMSO-d6): d = 7.63–7.71 (m, 3 H), 8.04 (d,
J = 7.1 Hz, 2 H), 8.80 (s, 2 H).
19F NMR (470 MHz, DMSO-d6): d = –83.36.
MS (EI, 70 eV): m/z (%) = 213 (7) [M]+, 195 (20) [M – H2O]+, 144
(17) [M – CF3]+, 126 (100) [M – H2O – CF3]+, 98 (12) [M – H2O –
COCF3]+, 72 (13), 71 (48), 69 (17) [CF3]+, 45 (34), 39 (33), 32 (28).
13C NMR (125 MHz, DMSO-d6): d = 89.4 (q, 2JCF = 34.0 Hz), 121.9
(q, 1JCF = 289.0 Hz), 122.6, 126.7, 129.6, 132.5, 162.7, 164.8.
1-(1,3-Benzothiazol-2-yl)-2,2,2-trifluoroethane-1,1-diol (7i)
White crystals; mp 104–111 °C.
19F NMR (470 MHz, DMSO-d6): d = –83.00.
1H NMR (500 MHz, DMSO-d6): d = 7.50 (t, J = 7.9 Hz, 1 H), 7.56
(t, J = 7.9 Hz, 1 H), 8.09 (d, J = 7.9 Hz, 1 H), 8.15 (d, J = 7.9 Hz, 1
H), 8.48 (s, 2 H).
1-(1,3-Benzothiazol-2-yl)-1-(benzylamino)-2,2,2-trifluoroeth-
anol (9)
A mixture of 4i (1 equiv) and BnNH2 (8; 1 equiv) in toluene was
heated for 5 min. The precipitate that formed was crystallized from
i-PrOH.
2
13C NMR (125 MHz, DMSO-d6): d = 92.0 (q, JCF = 32.5 Hz),
122.6, 122.8 (q, 1JCF = 289.7 Hz), 123.6, 126.1, 126.6, 135.3, 152.9,
169.5.
Yield 77%; mp 96–97 °C (dec).
19F NMR (470 MHz, DMSO-d6): d = –82.24.
MS (EI, 70 eV): m/z (%) = 249 (1) [M]+, 231 (77) [M – H2O]+, 162
(100) [M – H2O – CF3]+, 134 (76) [M – H2O – COCF3]+, 107 (15),
69 (30) [CF3]+, 63 (15).
1H NMR (500 MHz, DMSO-d6): d = 3.62 (m, 1 H), 3.82–3.94 (m,
2 H), 7.20 (t, J = 7.0 Hz, 1 H), 7.28 (dd, J = 7.0 Hz, 2 H), 7.36 (d,
J = 7.0 Hz, 2 H), 7.50 (dd, J = 8.0, 7.0 Hz, 1 H), 7.56 (dd, J = 8.0,
7.0 Hz, 1 H), 7.92 (br s, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 8.16 (d,
J = 8.0 Hz, 1 H).
2,2,2-Trifluoro-1-(5-phenyl-1,3-oxazol-2-yl)ethane-1,1-diol (7j)
White crystals; mp 99–103 °C.
13C NMR (125 MHz, DMSO-d6): d = 45.4, 86.4 (q, 2JCF = 29.8 Hz),
122.9, 123.8, 124.0 (q, 1JCF = 290.5 Hz), 126.3, 126.9, 127.2, 128.4,
128.5, 136.1, 140.3, 153.2, 170.0.
19F NMR (470 MHz, DMSO-d6): d = –78.89.
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

PAPER
2-(Trifluoroacetyl)imidazoles, -1,3-thiazoles, and -1,3-oxazoles
Crystal data for 7i
955
1-(4-Amino-3,5-dimethylphenyl)-1-(1,3-benzothiazol-2-yl)-
2,2,2-trifluoroethanol (11)
A mixture of 4i (1 equiv) and 2,6-dimethylaniline (10; 1 equiv) in
toluene was heated for 3 h at 100 °C. The precipitate that formed
was crystallized from i-PrOH.
C9H6NO2SF3, orthorhombic Pbca, a = 13.235(1) Å, b = 7.734(1) Å,
c = 18.735(1) Å, V = 1917.6(1) Å3, Z = 8, rcalcd = 1.726 g/cm3,
m(MoKa) = 0.366 mm–1, F(000) = 1008, 163 parameters,
R1 = 0.033, wR2 = 0.075 (1637 reflections, F > 4s), R1 = 0.068,
wR2 = 0.084 (2707 unique reflections), S = 0.880, Dr (min/
max) = –0.175/0.268 e·Å–3.
Beige crystals; yield: 25%; mp 222–223 °C
1H NMR (500 MHz, DMSO-d6): d = 2.05 (s, 6 H), 4.77 (s, 2 H), 7.10
(s, 2 H), 7.46 (dd, J = 6.5 Hz, 1 H), 7.53 (dd, J = 6.5 Hz, 1 H), 8.08
(m, 3 H).
13C NMR (125 MHz, DMSO-d6): d = 18.6, 78.3 (q, 2JCF = 28.9 Hz),
120.4, 122.7, 123.3, 123.8, 125.0 (q, 1JCF = 288.0 Hz), 126.1, 126.8,
126.8, 135.0, 145.5, 153.2, 173.0.
19F NMR (470 MHz, DMSO-d6): d = –75.88.
MS (EI, 70 eV): m/z (%) = 352 (22) [M]+, 283 (39) [M – CF3]+, 162
References
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Organofluorine Compounds in Medicinal Chemistry and
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(b) Kukhar V. P., Soloshonok V. A.; Fluorine-Containing
Amino Acids, Synthesis and Properties; Wiley: New York,
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T., Eds.; American Chemical Society: Washington D.C.,
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(2) (a) Lin, P.; Jiang, J. Tetrahedron 2000, 56, 3635; and
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Chem. Soc. 1964, 86, 4948. (b) For methyl trifluoro-
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(4) (a) Braun, R. A. J. Org. Chem. 1966, 31, 3828.
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(13), 119 (10), 148 (100), 136 (17), 120 (16).
2-(1,3-Benzothiazol-2-yl)-1,1,1-trifluoro-5-phenylpent-4-en-2-
ol (13)
A mixture of 4i (1 equiv) and allylbenzene (12; 3 equiv) was heated
in a pressure tube for 24 h at 130 °C. Excess 12 was then removed
at reduced pressure, and the product was purified by flash chroma-
tography.
Brown oil; yield: 64%.
1H NMR (500 MHz, DMSO-d6): d = 3.04–3.14 (m, 1 H), 3.20–3.30
(m, 1 H), 6.00–6.14 (m, 1 H), 6.48 (d, J = 15.6 Hz, 1 H), 7.10–7.32
(m, 5 H), 7.46 (dd, J = 8.0, 7.0 Hz, 1 H), 7.53 (dd, J = 8.0, 7.0 Hz,
1 H), 7.90 (s, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1
H)
13C NMR (125 MHz, DMSO-d6): d = 38.66, 77.88 (q, JCF = 27.7
Hz), 121.94, 122.79, 123.63, 125.12 (q, JCF = 288.0 Hz), 125.99,
126.38, 126.80, 127.92, 129.04, 134.85, 135.31, 137.03, 153.60,
171.19.
19F NMR (470 MHz, DMSO-d6): d = –78.16.
2
1
(5) Ohkura, H.; Berbasov, D. O.; Soloshonok, V. A.
Tetrahedron 2003, 59, 1647.
Single-Crystal X-ray Analyses
(6) (a) Chkanikov, N. D.; Sviridov, V. D.; Zelenin, A. E.;
Galakhov, M. V.; Kolomiets, A. F.; Fokin, A. V. Bull. Acad.
Sci. USSR, Div. Chem. Sci. (Engl. Transl.) 1990, 39, 323.
(b) Masciardi, R.; Kamer, M.; Nock, N. Eur. J. Org. Chem.
2003, 4286.
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J. Org. Chem. USSR (Engl. Transl.) 1991, 27, 641.
(b) Kobayashi, Y.; Nagai, T.; Kumadaki, I. Chem. Pharm.
Bull. 1984, 32, 5031. (c) Iseki, K.; Nagai, T.; Kobayashi, Y.
Chem. Pharm. Bull. 1992, 32, 1346. (d) Urry, W. H.; Niu, J.
H. Y.; Lundsted, L. G. J. Org. Chem. 1968, 33, 2302.
(8) (a) Golubev, A. S.; Kolomiets, A. F.; Fokin, A. V.
J. Fluorine Chem. 1991, 54, 273. (b) Golubev, A. S.;
Galakhov, M. V.; Kolomiets, A. F.; Fokin, A. V. Bull. Russ.
Acad. Sci., Div. Chem. Sci. (Engl. Transl.) 1992, 41, 2193.
(9) Lermontov, S. A.; Shkavrov, S. V.; Kuryleva, N. V.
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Unit cell parameters and intensities of all sets of reflections were
measured on an Xcalibur-3 diffractometer (CCD detector,
l(MoKa) irradiation, w-scans) All structures were solved by direct
methods by use of the SHELXTL package.18 Positions of the hydro-
gen atoms were located from difference maps of the electron densi-
ty and refined within isotropic approximation (4n, 7i) or by use of a
riding model (5j). Atomic coordinates and crystallographic param-
eters were deposited at the Cambridge Crystallographic Data Centre
under CCDC 662987-662989.
Crystal Data for 4n
C9H5N2OF3, monoclinic, P21/m, a = 8.001(1) Å, b = 6.699(1) Å,
c = 8.262(1) Å, b = 93.98(1)°, V = 441.69(4) Å3, Z = 2, rcalcd = 1.61
g/cm3, m = 0.151 mm–1, F(000) = 216, 103 parameters, R1 = 0.038,
wR2 = 0.1077 (779 reflections, F > 4s), R1 = 0.052, wR2 = 0.1155
(1092 unique reflections), S = 1.144, Dr (min/max) = –0.151/0.163
e Å–3.
(10) (a) Regel, E.; Büchel, K. H. Justus Liebigs Ann. Chem. 1977,
145. (b) Kawase, M.; Sakagami, H.; Kusama, K.;
Motohashi, N.; Saito, S. Bioorg. Med. Chem. Lett. 1999, 9,
3113. (c) Fujii, S.; Maki, Y.; Kimoto, H. J. Fluorine Chem.
1987, 35, 437. (d) Salvador, R. L.; Saucier, M. Tetrahedron
1971, 27, 1221.
Crystal Data for 5g
C8H9N6OF3, monoclinic, P21/n, a = 9.6712(3) Å, b = 10.3909(3) Å,
c = 11.4583(4) Å, b = 100.10(1)°, V = 1133.63(6) Å3, Z = 4,
r
calcd = 1.536 g/cm3, m = 0.142 mm–1, F(000) = 536, 169 parame-
ters, R1 = 0.039, wR2 = 0.090 (1481 reflections,
F > 4s),
R1 = 0.0785, wR2 = 0.1032 (2529 unique reflections), S = 0.893, Dr
(min/max) = –0.164/0.216 e·Å–3.
Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York

956
P. V. Khodakovskiy et al.
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Synthesis 2008, No. 6, 948–956 © Thieme Stuttgart · New York