Acylation of primary polyfluoroalkanethioamides

Article abstract of DOI:10.1016/j.jfluchem.2012.05.008

The reaction conditions and the nature of acyl chloride strongly influence the outcome of the primary polyfluoroalkanethioamides acylation. Preparation of NH-acetyl polyfluoroalkanethioamides was achieved conducting the reactions in acetonitrile at -20°C in the presence of pyridine. The reactions of polyfluoroalkanethioamides with 5-hydroperfluoropentanoyl chloride are efficient for the synthesis of NH-acyl derivatives when they were carried out in the absence of a base under heating at 100°C. The obtained NH-acyl polyfluoroalkanethioamides enter into cycloaddition reactions with 2,3-dimethylbutadiene at room temperature.

Full text of DOI:10.1016/j.jfluchem.2012.05.008

Journal of Fluorine Chemistry 140 (2012) 76–81
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Acylation of primary polyfluoroalkanethioamides
*
Sergiy S. Mykhaylychenko, Nadiia V. Pikun, Yuriy G. Shermolovich
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5, Murmanska, 02094 Kiev, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
The reaction conditions and the nature of acyl chloride strongly influence the outcome of the primary
polyfluoroalkanethioamides acylation. Preparation of NH-acetyl polyfluoroalkanethioamides was
achieved conducting the reactions in acetonitrile at ꢀ20 8C in the presence of pyridine. The reactions
of polyfluoroalkanethioamides with 5-hydroperfluoropentanoyl chloride are efficient for the synthesis of
NH-acyl derivatives when they were carried out in the absence of a base under heating at 100 8C. The
obtained NH-acyl polyfluoroalkanethioamides enter into cycloaddition reactions with 2,3-dimethylbu-
tadiene at room temperature.
Received 11 April 2012
Received in revised form 7 May 2012
Accepted 8 May 2012
Available online 16 May 2012
Keywords:
Fluorinated thioamide
Acylation
ß 2012 Elsevier B.V. All rights reserved.
Acyl chloride
Disulfide
Cycloaddition
1. Introduction
2. Results and discussion
Thioamides have found a wide variety of synthetic applications
over the past decades [1]. Divergent transformations of these
compounds employed in organic synthesis arise from the high
versatility of the thioamide functionality. At the same time, the
additional functionalization of thioamides offers new synthetic
possibilities. Among a large number of aliphatic, aromatic and
heterocyclic derivatives, fluorinated thioamides remain poorly
investigated, although reported procedures indicate their promis-
ing synthetic potential as fluorine-containing building-blocks [2].
Recently, we have described novel protocols for the reactions of
N,N-dialkyl- or N-alkyl(aryl)-polyfluoroalkanethioamides with
2,3-dimethyl-butadiene [2e] and trialkyl phosphites [2f]. These
reactions were shown to occur under drastic conditions, therefore
we decided to increase the reactivity of the thiocarbonyl group by
introducing an electron-withdrawing substituent, such as an acyl
group, at the nitrogen atom of thioamide.
Our initial experiments have shown that the outcome of the
acylation of primary polyfluoroalkanethioamides 1a–c [10]
strongly depends on the reaction conditions (solvent, tempera-
ture, base) and the nature of acyl chlorides. The treatment of
thioamides 1a,c with acetyl-, benzoyl-, 5-hydroperfluoropenta-
noyl chlorides in different solvents (diethyl ether, dichloro-
methane, acetonitrile) at 0 8C in the presence of triethylamine led
to complex mixtures of products which hardly undergo any
separation and purification.
We have found that the reaction of trifluorothioacetamide 1a
with acetyl chloride in acetonitrile at ꢀ20 8C in the presence of
pyridine afforded 1,3-dithiethane 3 as a mixture of two stereo-
isomers (the ratio is 85:15 according to 19F NMR) (Scheme 1).
Obviously, the dimerization of the intermediary NH-acetyl
thioamide 2a resulted in the formation of compound 3. NMR
(
19F, 1H, 13C) and MS data are consistent with the dimeric structure
Among the methods of the synthesis of non-fluorinated NH-acyl
thioamides [3–9], the direct acylation provides good yields for NH-
alkanoyl derivatives [3–6], and we have chosen it for the
preparation of fluorinated analogs.
To the best of our knowledge, the acylation of polyfluoroalk-
anethioamides has been described only for N-methyl trifluor-
othioacetamide [2a]. In the present paper, we report on the
investigation of the reactions between unsubstituted polyfluor-
oalkanethioamides and acyl chlorides.
of 3. It should be noted that only a few examples of spontaneous
dimerization of fluorinated thiocarbonyl compounds such as
hexafluorothioacetone, perfluorobutane-2-thione, chlorodifluor-
othioacetyl chloride and trifluoromethyl trifluorodithioacetate
have been reported in the literature [11].
In contrast to trifluorothioacetamide 1a, thioamides 1b,c
reacted with acetyl chloride giving NH-acetyl derivatives 2b,c in
good yields (Scheme 1).
As opposed to above mentioned reactions, the treatment of
thioamides 1a–c with 5-hydroperfluoropentanoyl chloride gave
mixtures of products. These reactions were carried out in the
absence of a base under heating at 100 8C affording NH-acyl
derivatives 4a–c in high yields (Scheme 2).
* Corresponding author. Tel.: +380 44 2928312; fax: +380 44 5732643.
E-mail address: sherm@ioch.kiev.ua (Y.G. Shermolovich).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.05.008

S.S. Mykhaylychenko et al. / Journal of Fluorine Chemistry 140 (2012) 76–81
77
H3C
O
F3C
HN
S
S
NH
CF3
S
O
CH3
O
RF = CF3
F3C
N
H
CH3
H3C
O
F3C
HN
S
S
NH
O
2a
CF3
H3C
Cl
S
CH3
O
RF
NH2
3
(85:15)
Py, MeCN, -20 °C
(35%)
RF = CF3
1a
RF = H(CF2)2
RF = C3F7
S
O
1b
1c
N
H
CH3
RF
RF = H(CF2)2,
C3F7
RF = H(CF2)2
RF = C3F7
2b
(70%)
2c
O
(65%)
Scheme 1.
O
H(CF2)4
Cl
S
S
RF
N
H
(CF2)4H
RF
NH2
100 °C, 1h
RF = CF3
F = H(CF 2)2
1a
RF = CF3
4a
(84%)
R
1b
1c
RF = H(CF 2)2
RF = C3F7
4b
4c
(94%)
(95%)
RF = C3F7
Scheme 2.
H(CF2)4
O
H(CF2)4
O
S
O
S
S
F3C
HN
S
S
NH
CF3
F3C
HN
NH
100 °C
40 h
F3C
N
H
(CF2)4H
CF3
(CF2)4H
(CF2)4H
O
O
4a
5
(55:45)
(31%)
Scheme 3.
In the 13C NMR spectra of NH-acyl thioamides 2b,c and 4a–c the
signals in the ranges of 178.4–186.5 ppm and 155.1–170.3 ppm
were attributed to the C55S and C55O groups, respectively.
Compounds 4b,c appeared to be stable at room temperature,
while trifluoromethyl-substituted NH-acyl thioamide 4a slowly
undergoes dimerization into a mixture of stereoisomeric 1,3-
dithiethane 5 (the ratio is 55:45 according to 19F NMR). The total
conversion of 4a to 5 was achieved by heating the compound 4a at
100 8C for 40 h (Scheme 3).
In contrast to the reactions of thioamides 1a–c with 5-hydro-
perfluoropentanoyl chloride, heating a mixture of trifluorothioa-
cetamide 1a with benzoyl chloride at 100 8C for 13 h resulted in the
formation of new fluorine-containing disulfide 6a (Scheme 4). The
reaction with benzoyl chloride was extended to other thioamides
1b,c and proceeded in the same manner with cyclopropanoyl
chloride giving compounds 6a–d (Scheme 4).
NMR (19F, 1H, 13C) and MS data of compounds 6a–d are in good
agreement with the proposed structures. In the 13C NMR spectra of

78
S.S. Mykhaylychenko et al. / Journal of Fluorine Chemistry 140 (2012) 76–81
O
O
R
R
S
S
Cl
S
RF
RF
O
R
NH2
HN
100 °C, 13-25 h
RF = CF3
R = Ph
6a
RF = CF3
1a
(50%)
RF = H(CF 2)2 R = Ph
RF = H(CF 2)2
RF = C3F7
6b
6c
6d
1b
1c
(34%)
(77%)
(30%)
RF = C3F7
F = C3F7
R = Ph
R
R = c-Pr
Scheme 4.
S
O
path A
O
O
R
N
R
R
RF
H
8
S
Cl
S
RF
RF
NH2
NH
O
9
RF
N
1a-c
R
SH
path B
7
10
O
R
O
S
O
S
S
R
SH
N
H
R
RF
RF
O
R
HN
9
8
6a-d
Scheme 5.
disulfides 6a–d the signals observed in the ranges of 166.5–
173.4 ppm and 189.5–197.7 ppm are characteristic of an amide
and thioester function, correspondingly [12]. In the 19F NMR
spectra of 6b–d fluorine atoms of the CF2 group attached to the
asymmetric carbon atom were identified as an AB-system.
We propose the following scheme for the formation of
disulfides 6a–d (Scheme 5). The initially formed S-acyl inter-
mediates 7 can undergo transformations into two pathways.
According to the pathway A, rearrangement of 7 gave NH-acyl
thioamides 8. It should be noted that the formation of S-acyl
derivatives and their transformation into N-acyl compounds in the
reactions of non-fluorinated thioamides with acyl chlorides was
demonstrated by Walter and Saha [13]. Pathway B includes the
elimination of nitriles and the formation of thiocarboxylic acid 9.
Such a reaction pathway was proposed by Goerdeler et al. for the
reaction of benzamide with aromatic acid chlorides [3]. The
thiophilic addition of thiocarboxylic acid 9 to NH-acyl thioamides 8
gives final disulfides 6a–d.
As other thiocarbonyl compounds containing polyfluoroalkyl
groups [14], NH-acyl thioamides 4a–c, 2c are active dienophiles
S
S
O
RF
NH
N
H
R
RF
CHCl3, rt
O
R
R = H(CF 2)4
R = H(CF 2)4 4a
RF = CF3
F = H(CF 2)2
11a
R
R
F = CF3
F = H(CF 2)2
(62%)
R
4b
4c
R = H(CF 2)4
R = H(CF 2)4
R = CH 3
11b
11c
R = H(CF 2)4
R = H(CF 2)4
R = CH 3
(50%)
(53%)
RF = C3F7
F = C3F7
RF = C3F7
RF = C3F7
2c
R
11d
(72%)
Scheme 6.

S.S. Mykhaylychenko et al. / Journal of Fluorine Chemistry 140 (2012) 76–81
79
and readily react with 2,3-dimethylbutadiene to afford new
thiopyran derivatives 11a–d (Scheme 6).
110.7 (tt, 1JC,F = 269.2 Hz, 2JC,F = 28.2 Hz, CF2), 170.0 (s, C55O), 186.5
2
(t, JC,F = 23.5 Hz, C55S). MS: m/z = 202 [Mꢀ1]. Anal. Calcd. for
In conclusion, we have shown that the outcome of the acylation
reactions of primary polyfluoroalkanethiocarboxylic acid amides
depends on the reaction conditions and the nature of acyl chloride.
The reactions of polyfluoroalkanethioamides with benzoyl- and
cyclopropanonyl chlorides in the absence of a base afforded novel
fluorine-containing disulfide derivatives, while the use of 5-
hydroperfluoropentanoyl chloride allowed obtaining NH-acyl
thioamides. Preparation of NH-acetyl derivatives was achieved
conducting the reaction in acetonitrile at ꢀ20 8C in the presence of
pyridine. The obtained NH-acyl thioamides are more reactive in
cycloaddition reactions with 2,3-dimethylbutadiene as compared
with primary and N-alkyl(aryl) polyfluoroalkanethioamides which
react under drastic conditions.
C5H5F4NOS: C, 29.6; H, 2.5; N, 6.9; S, 15.8. Found: C, 29.7; H, 2.6; N,
6.7; S, 15.9.
3.1.3. N-(2,2,3,3,4,4,4-Heptafluorobutanethioyl)acetamide (2c)
Yield: 65%. Pink solid. mp 70–72 8C. 1H NMR (CDCl3,
d ppm):
2.59 (s, 3H, CH3), 9.51 (bs, 1H, NH). 19F NMR (CDCl3,
d
ppm): ꢀ81.3
(m, 3F, CF3), ꢀ112.4 (m, 2F, CF2), ꢀ125.9 (m, 2F, CF2). 13C NMR
(CDCl3, d ppm): 26.5 (s, CH3), 107.0–119.5 (m, CF3CF2CF2), 170.3 (s,
2
C55O), 181.8 (t, JC,F = 25.4 Hz, C55S). MS: m/z = 270 [Mꢀ1]. Anal.
Calcd. for C6H4F7NOS: C, 26.6; H, 1.5; N, 5.2; S, 11.8. Found: C, 26.8;
H, 1.8; N, 5.2; S, 11.9.
3.2. General procedure for the reaction of polyfluoroalkanethioamides
(1a–c) with 2,2,3,3,4,4,5,5-octafluoropentanoyl chloride
3. Experimental
A mixture of polyfluoroalkanethioamide (1a–c) (10.0 mol, 1.0
equiv.) and 2,2,3,3,4,4,5,5-octafluoropentanoyl chloride (30.0 mol,
3.0 equiv.) was heated at 100 8C for 1 h. The crude product was
purified by fractional distillation to give the corresponding NH-acyl
derivative (4a–c).
The 1H, 13C and 19F NMR spectra were recorded on a Varian-
VXR-300 instrument at 299.9, 75.4 and 282.2 MHz, respectively.
Tetramethylsilane (1H NMR:
d = 0.00 ppm), CHCl3 (
13C NMR:
d
= 77.16 ppm), C6F6
(
19F NMR:
d
= ꢀ162.9 ppm) were used as
internal standards for 1H, 13C and 19F NMR spectra. MS data were
obtained on ADSI MS, Agilent 1100\DAD\MSD VL G1965 instru-
ment. UV–visible spectra were recorded on a SHIMADZU UV-3110
spectrophotometer.
3.2.1. 2,2,3,3,4,4,5,5-Octafluoro-N-(2,2,2-
trifluoroethanethioyl)pentanamide (4a)
Yield: 84%. Deep red liquid. bp 68–70 8C (0.08 mmHg). 1H NMR
2
3
The progress of all reactions was monitored by 19F NMR
(CDCl3,
d
ppm): 6.11 (tt, JH,F = 51.8 Hz, JH,F = 5.1 Hz, 1H, HCF2),
ppm): ꢀ71.0 (m, 3F, CF3),
spectroscopy. Silica gel Merck 60 (40–63
m
m) was used for column
9.97 (bs, 1H, NH). 19F NMR (CDCl3,
d
chromatography. Elemental analysis was performed in Analytical
Laboratory of the Institute of Organic chemistry, NAS of Ukraine.
ꢀ121.1 (m, 2F, CF2), ꢀ125.5 (m, 2F, CF2), ꢀ130.6 (m, 2F, CF2),
ꢀ140.3 (dm, JF,H = 51.8 Hz, 2F, HCF2). 13C NMR (CDCl3,
d ppm):
2
1
104.0–114.0 (m, 4 ꢁ CF2), 115.5 (q, JC,F = 279.4 Hz, CF3), 155.3 (t,
2JC,F = 28.4 Hz, C55O), 179.1 (q, 2JC,F = 38.0 Hz, C55S). MS: m/z = 356
[Mꢀ1]. Anal. Calcd. for C7H2F11NOS: C, 23.6; H, 0.6; N, 3.9; S, 9.0.
Found: C, 23.6; H, 0.7; N, 3.7; S, 9.2.
3.1. General procedure for the reaction of polyfluoroalkanethioamides
(1a–c) with acetyl chloride
A
solution of acetyl chloride (21.0 mmol, 1.4 eqiuv.) in
acetonitrile (10 mL) was added dropwise at ꢀ20 8C under argon
atmosphere to a solution of the corresponding polyfluoroalk-
anethioamide (15.0 mmol, 1.0 eqiuv.) (1a–c) and pyridine
(21.0 mmol, 1.4 eqiuv.) in acetonitrile (40 mL). The reaction
mixture was stirred at ꢀ20 8C for 0.5 h and then for 16 h at room
temperature. The solvent was evaporated in vacuo at room
temperature and diethyl ether (50 mL) was added to the residue.
In the case of the isolation of compound (3), the precipitate formed
was filtered off, washed with water (10 mL) and dried. For the
isolation of compounds (2b,c) the precipitate was filtered off and
the filtrate was washed with water (3 ꢁ 10 mL). The organic layer
was separated, dried over Na2SO4 and concentrated in vacuo giving
NH-acetyl derivatives (2b,c).
3.2.2. 2,2,3,3,4,4,5,5-Octafluoro-N-(2,2,3,3-
tetrafluoropropanethioyl)pentanamide (4b)
Yield: 94%. Deep red liquid. bp 37–38 8C (0.08 mmHg). UV
(hexane, nm):
l d ppm): 6.10 (tt,
max = 271. 1H NMR (CDCl3,
3
2
2JH,F = 51.7 Hz, JH,F = 5.1 Hz, 1H, HCF2), 6.27 (tt, JH,F = 53.0 Hz,
3JH,F = 5.1 Hz, 1H, HCF2), 10.22 (bs, 1H, NH). 19F NMR (CDCl3,
d
ppm): ꢀ118.9 (m, 2F, CF2), ꢀ122.1 (m, 2F, CF2), ꢀ125.5 (m, 2F, CF2),
ꢀ130.1 (m, 2F, CF2), ꢀ138.6 (m, 4F, 2 ꢁ HCF2). 13C NMR (CDCl3,
d
2
ppm): 105.0–113.5 (m, 6 ꢁ CF2), 155.2 (t, JC,F = 28.2 Hz, C55O),
183.9 (t, 2JC,F = 27.0 Hz, C55S). MS: m/z = 388 [Mꢀ1]. Anal. Calcd. for
C8H3F12NOS: C, 24.7; H, 0.8; N, 3.6; S, 8.2. Found: C, 24.7; H, 0.8; N,
3.6; S, 8.3.
3.2.3. 2,2,3,3,4,4,5,5-Octafluoro-N-(2,2,3,3,4,4,4-
heptafluorobutanethioyl)-pentanamide (4c)
3.1.1. N,N0-[2,4-Bis(trifluoromethyl)-1,3-dithitane-2,4-
diyl]diacetamide (3)
Yield: 95%. Deep red liquid. bp 40–42 8C (0.08 mmHg). 1H NMR
2
3
Yield: 35%. Colorless solid. Mixture of stereoisomers (the ratio is
(CDCl3,
d ppm): 6.09 (tt, JH,F = 51.9 Hz, JH,F = 5.1 Hz, 1H, HCF2),
85:15 according to 19F NMR). 1H NMR (DMSO-d6,
d
ppm): 1.96 (s,
10.00 (bs, 1H, NH). 19F NMR (CDCl3,
d
ppm): ꢀ81.4 (t, 3JF,F = 13.0 Hz,
3H, CH3), 10.07 (bs, 1H, NH). 19F NMR (DMSO-d6,
d
ppm): ꢀ78.7 (m,
3F, CF3), ꢀ113.2 (m, 2F, CF2), ꢀ122.1 (m, 2F, CF2), ꢀ125.5 (m, 2F,
3F, CF3 major), ꢀ80.4 (m, 3F, CF3 minor). 13C NMR (DMSO-d6,
d
CF2), ꢀ126.4 (m, 2F, CF2), ꢀ130.0 (m, 2F, CF2), ꢀ138.3 (dm,
2
ppm): 22.4 (s, CH3), 56.8 (q, JC,F = 36.8 Hz, CCF3), 123.7 (q,
1JC,F = 284.2 Hz, CF3), 169.9 (s, C55O). MS: m/z = 343 [M+1]. Anal.
Calcd. for C8H8F6N2O2S2: C, 28.1; H, 2.4; N, 8.2; S, 18.7. Found: C,
28.1; H, 2.5; N, 8.1; S, 18.7.
2JF,H = 51.9 Hz, 2F, HCF2). 13C NMR (CDCl3,
d
ppm): 105.0–115.0 (m,
1
2
6 ꢁ CF2), 117.4 (q, JC,F = 288.1 Hz, CF3), 155.1 (t, JC,F = 28.2 Hz,
2
C55O), 178.4 (t, JC,F = 26.7 Hz, C55S). MS: m/z = 456 [Mꢀ1]. Anal.
Calcd. for C9H2F15NOS: C, 23.7; H, 0.4; N, 3.1; S, 7.0. Found: C, 23.8;
H, 0.5; N, 2.9; S, 7.1.
3.1.2. N-(2,2,3,3-Tetrafluoropropanethioyl)acetamide (2b)
Yield: 70%. Yellow-red crystals. mp 59–62 8C. 1H NMR (CDCl3,
ppm): 2.58 (s, 3H, CH3), 6.37 (tt, JH,F = 53.1 Hz, JH,F = 5.4 Hz, 1H,
d
3.3. Dimerization of 2,2,3,3,4,4,5,5-octafluoro-N-(2,2,2-trifluoro-
2
3
ethanethioyl)pentanamide (4a)
HCF2), 9.70 (bs, 1H, NH). 19F NMR (CDCl3,
d
ppm): ꢀ119.2 (m, 2F,
2
CF2), ꢀ139.4 (dm, JF,H = 53.1 Hz, 2F, HCF2). 13C NMR (CDCl3,
d
2,2,3,3,4,4,5,5-Octafluoro-N-(2,2,2-trifluoro-ethanethioyl)pen-
tanamide (4a) (0.50 g, 1.4 mmol) was heated at 100 8C for 40 h. The
ppm): 26.6 (s, CH3), 109.4 (tt, 1JC,F = 252.4 Hz, 2JC,F = 32.9 Hz, HCF2),

80
S.S. Mykhaylychenko et al. / Journal of Fluorine Chemistry 140 (2012) 76–81
crude product was recrystallized from hexane to give the
compound (5).
CF3CF2CF2), 127.4 (s, 2 ꢁ CH, Ph), 128.0 (s, 2 ꢁ CH, Ph), 128.8 (s,
2 ꢁ CH, Ph), 129.1 (s, 2 ꢁ CH, Ph), 132.1 (s, Cq, Ph,), 132.6 (s, CH, Ph),
134.81 (s, Cq, Ph), 134.83 (s, CH, Ph), 166.5 (s, CONH), 189.5 (s, COS).
MS: m/z = 472 [M+1]. Anal. Calcd. for C18H12F7NO2S2: C, 45.9; H,
2.6; N, 3.0; S, 13.6. Found: C, 46.1; H, 2.6; N, 3.2; S, 13.4.
3.3.1. N,N0-[2,4-Bis(trifluoromethyl)-1,3-dithitane-2,4-
diyl]bis(2,2,3,3,4,4,5,5-octafluoropentanamide) (5)
Yield: 31%. Colorless solid. Mixture of stereoisomers (the ratio is
55:45 according to 19F NMR). 1H NMR (DMSO-d6,
d
ppm): 7.07 (tm,
3.4.4. N-{1-[(Cyclopropylcarbonyl)dithio]-2,2,3,3,4,4,4-
2JH,F = 50.4 Hz, 2H, 2 ꢁ HCF2), 11.96 (bs, 2H, 2 ꢁ NH). 19F NMR
heptafluorobutyl}cyclo-propane-carboxamide (6d)
(Et2O,
d
ppm): ꢀ80.9 (m, 3F, CF3 major), ꢀ82.5 (m, 3F, CF3 minor),
Yield: 30%. Colorless solid. mp 105–108 8C. 1H NMR (CDCl3,
d
ꢀ121.3 (m, 2F, CF2), ꢀ126.1 (m, 2F, CF2), ꢀ131.1 (m, 2F, CF2),
ppm): 0.84 (m, 2H, cyclopropyl), 1.04 (m, 2H, cyclopropyl), 1.14 (m,
2H, cyclopropyl), 1.29 (m, 2H, cyclopropyl), 1.34 (m, 2H,
ꢀ140.3 (dm, 2JF,H = 50.4 Hz, 2F, HCF2). 13C NMR (DMSO-d6,
d ppm):
2
3
55.5 (q, JC,F = 37.3 Hz, CCF3), 105.5–113.0 (m, 4 ꢁ CF2), 123.3 (q,
1JC,F = 283.3 Hz, CF3), 156.8 (t, 2JC,F = 27.5 Hz, C55O major), 157.3 (t,
2JC,F = 27.5 Hz, C55O minor). MS: m/z = 356 [(M/2)ꢀ1]. Anal. Calcd.
for C14H4F22N2O2S2: C, 23.5; H, 0.6; N, 3.9; S, 9.0. Found: C, 23.7; H,
0.5; N, 4.0; S, 9.2.
cyclopropyl), 2.22 (m, 2H, cyclopropyl), 5.97 (ddd, JH,F = 14.8 Hz,
3
3
3JH,H = 10.3 Hz, JH,F = 5.3 Hz, 1H, CH), 6.15 (d, JH,H = 10.3 Hz, 1H,
NH). 19F NMR (CDCl3,
d
ppm): ꢀ81.9 (m, 3F, CF3), ꢀ114.0 (dm,
2JF,F = 285.2 Hz, 1F, CFAFB), ꢀ121.5 (dm, 2JF,F = 285.2 Hz, 1F, CFAFB),
ꢀ126.5 (m, 2F, CF2). 13C NMR (CDCl3,
d ppm): 8.3 (s, CH2,
cyclopropyl), 8.7 (s, CH2, cyclopropyl), 12.7 (s, 2 ꢁ CH2, cyclopro-
3.4. General procedure for the synthesis of disulfides (6a–d)
pyl), 14.4 (s, CH, cyclopropyl), 21.1 (s, CH, cyclopropyl), 57.0 (dd,
2
2JC,F = 30.6 Hz, JC,F = 22.1 Hz, CH), 108.8–119.0 (m, CF3CF2CF2),
A mixture of polyfluoroalkanethioamide (1a–c) (20.0 mmol, 1.0
eqiuv.) and the corresponding acyl chloride (40.00 mmol, 2.0
eqiuv.) was heated at 100 8C for 13–25 h. After the completion of
the reaction, the excess of acyl chloride was removed in vacuo
(0.08 mmHg). The crude product was purified by recrystallization
from ethanol. N-[1-(benzoyldithio)-2,2,3,3-tetrafluoro-propyl]-
benzamide (6b) was purified by column chromatography on silica
gel (eluent:mixture (70:30) of ethyl acetate and hexane).
173.4 (s, CONH), 197.7 (s, COS). MS: m/z = 400 [M+1]. Anal. Calcd.
for C12H12F7NO2S2: C, 36.1; H, 3.0; N, 3.5; S, 16.0. Found: C, 36.1; H,
3.2; N, 3.8; S, 16.3.
3.5. General procedure for cycloaddition reaction of the compounds
(2c, 4a–c)
2,3-Dimethylbutadiene (2.0 mmol, 1.0 equiv.) was added to a
solution of compound (2c, 4a–c) (2.0 mmol, 1.0 equiv.) in
chloroform (10 mL). The reaction mixture was stirred at room
temperature for 2 h. The solvent was evaporated in vacuo and the
crude product was purified by chromatography on silica gel
(eluent:mixture (70:30) of hexane and ethyl acetate) to afford
thiopyran (11a–d).
3.4.1. N-[1-(Benzoyldithio)-2,2,2-trifluoroethyl]benzamide (6a)
Yield: 50%. Colorless solid. mp 160–163 8C. 1H NMR (CDCl3,
ppm): 6.04 (dq, JH,H = 10.0 Hz, JH,F = 7.0 Hz, 1H, CH), 6.86 (d,
3JH,H = 10.0 Hz, 1H, NH), 7.43 (m, 4H, Ph), 7.52 (t, 3JH,H = 7.6 Hz, 1H,
d
3
3
3
3
Ph), 7.62 (t, JH,H = 7.6 Hz, 1H, Ph), 7.75 (d, JH,H = 7.6 Hz, 2H, Ph),
7.83 (d, JH,H = 7.6 Hz, 2H, Ph). 19F NMR (CDCl3,
3JF,H = 7.0 Hz, 3F, CF3). 13C NMR (DMSO-d6,
d
ppm): ꢀ73.8 (d,
3
d
ppm): 59.0 (q,
3.5.1. N-[4,5-Dimethyl-2-(trifluoromethyl)-3,6-dihydro-2H-
2JC,F = 33.6 Hz, CH), 123.5 (q, 1JC,F = 278.6 Hz, CF3), 127.4 (s, 2 ꢁ CH,
Ph), 127.8 (s, 2 ꢁ CH, Ph), 128.2 (s, 2 ꢁ CH, Ph), 129.0 (s, 2 ꢁ CH,
Ph), 130.8 (s, Cq, Ph), 132.5 (s, CH, Ph), 134.5 (s, Cq, Ph), 134.6 (s, CH,
Ph), 166.8 (s, CONH), 187.0 (s, COS). MS: m/z = 372 [M+1]. Anal.
Calcd. for C16H12F9NO2S2: C, 51.7: H, 3.3; N, 3.8; S, 17.3. Found: C,
51.9; H, 3.3; N, 4.0; S, 17.4.
thiopyran-2-yl]-2,2,3,3,4,4,5,5-octafluoropentanamide (11a)
Yield: 62%. Colorless oil. 1H NMR (CDCl3,
d ppm): 1.74 (s, 3H,
CH3), 1.76 (s, 3H, CH3), 2.70 (d, 2JH,H = 16.4 Hz, 1H, CHAHB), 3.14 (d,
2
2JH,H = 16.6 Hz, 1H, SCHAHB), 3.34 (d, JH,H = 16.4 Hz, 1H, CHAHB),
2
2
3.57 (d, JH,H = 16.6 Hz, 1H, SCHAHB), 6.10 (tt, JH,F = 51.8 Hz,
3JH,F = 5.4 Hz, 1H, HCF2), 6.32 (bs, 1H, NH). 19F NMR (CDCl3,
d
2
ppm): ꢀ79.3 (m, 3F, CF3), ꢀ120.7 (dm, JF,F = 273.6 Hz, 1F, CFAFB),
3.4.2. N-[1-(Benzoyldithio)-2,2,3,3-tetrafluoropropyl]benzamide
ꢀ122.3 (dm, 2JF,F = 273.6 Hz, 1F, CFAFB), ꢀ126.9 (m, 2F, CF2), ꢀ130.5
2
2
(6b)
(dm, JF,F = 288.8 Hz, 1F, CFAFB), ꢀ132.3 (dm, JF,F = 288.8 Hz, 1F,
Yield: 34%. Colorless solid. mp 95–97 8C. 1H NMR (CDCl3,
d
CFAFB), ꢀ139.1 (dm, JF,H = 51.8 Hz, 2F, HCF2). 13C NMR (CDCl3,
d
2
3
3
ppm): 6.01 (dt, JH,F = 14.3 Hz, JH,H = 10.0 Hz, 1H, CH), 6.33 (tt,
2JH,F = 53.0 Hz, 3JH,F = 4.7 Hz, 1H, HCF2), 6.84 (d, 3JH,H = 10.0 Hz, 1H,
ppm): 18.7 (s, CH3), 19.7 (s, CH3), 30.1 (s, SCH2), 33.3 (s, CH2), 67.5
(q, 2JC,F = 23.0 Hz, CCF3), 105.1–119.4 (m, CF3, 4 ꢁ CF2), 123.3 (s, Cq),
3
2
NH), 7.43 (m, 4H, Ph), 7.52 (t, JH,H = 7.2 Hz, 1H, Ph), 7.62 (t,
124.7 (s, Cq), 156.7 (t, JC,F = 26.4 Hz, C55O). MS: m/z = 438 [Mꢀ1].
3JH,H = 7.2 Hz, 1H, Ph), 7.76 (d, JH,H = 7.2 Hz, 2H, Ph), 7.84 (d,
Anal. Calcd. for C13H12F11NOS: C, 35.5; H, 2.8; N, 3.2; S, 7.3. Found:
C, 35.6; H, 2.8; N, 3.3; S, 7.5.
3
3JH,H = 7.2 Hz, 2H, Ph). 19F NMR (CDCl3,
d
ppm): ꢀ122.3 (dm,
2JF,F = 268.7 Hz, 1F, CFAFB), ꢀ124.1 (dm, 2JF,F = 268.7 Hz, 1F, CFAFB),
2
ꢀ138.6 (dm, JF,H = 53.0 Hz, 2F, HCF2). MS: m/z = 404 [M+1]. Anal.
3.5.2. N-[4,5-Dimethyl-2-(1,1,2,2-tetrafluoroethyl)-3,6-dihydro-2H-
Calcd. for C17H13F4NO2S2: C, 50.6; H, 3.3; N, 3.5; S, 15.9. Found: C,
50.9; H, 3.5; N, 3.8; S, 16.0.
thiopyran-2-yl]-2,2,3,3,4,4,5,5-octafluoropentanamide (11b)
Yield: 50%. Yellow oil. 1H NMR (CDCl3,
d
ppm): 1.73 (s, 3H, CH3),
2
1.76 (s, 3H, CH3), 2.73 (d, JH,H = 16.4 Hz, 1H, CHAHB), 3.13 (d,
2
3.4.3. N-[1-(Benzoyldithio)-2,2,3,3,4,4,4-
2JH,H = 16.6 Hz, 1H, SCHAHB), 3.36 (d, JH,H = 16.4 Hz, 1H, CHAHB),
2
2
heptafluorobutyl]benzamide (6c)
3.51 (d, JH,H = 16.6 Hz, 1H, SCHAHB), 6.10 (tm, JH,F = 52.1 Hz, 2H,
Yield: 77%. Colorless solid. mp 100–103 8C. IR (KBr, cmꢀ1): 3300
2 ꢁ HCF2), 6.40 (bs, 1H, NH). 19F NMR (CDCl3,
ppm): ꢀ120.1 (dm,
d
(NH), 1666 (NHCOPh), 1553 (SCOPh). 1H NMR (CDCl3,
d
ppm): 6.28
2JF,F = 275.4 Hz, 1F, CFAFB), ꢀ121.8 (dm, 2JF,F = 275.4 Hz, 1F, CFAFB),
ꢀ123.4 (dm, 2JF,F = 273.5 Hz, 1F, CFAFB), ꢀ125.0 (dm,
2JF,F = 273.5 Hz, 1F, CFAFB), ꢀ126.4 (m, 2F, CF2), ꢀ130.0 (dm,
2JF,F = 290.2 Hz, 1F, CFAFB), ꢀ131.9 (dm, 2JF,F = 290.2 Hz, 1F, CFAFB),
ꢀ134.9 (m, 2F, CF2), ꢀ138.7 (dm, 2JF,H = 52.1 Hz, 2F, HCF2). 13C NMR
(ddd, 3JH,F = 14.8 Hz, 3JH,H = 10.4 Hz, 3JH,F = 5,2 Hz, 1H, CH), 6.85 (d,
3JH,H = 10.4 Hz, 1H, NH), 7.38 (m, 4H, Ph), 7.48 (t, 3JH,H = 7.6 Hz, 1H,
3
3
Ph), 7.59 (t, JH,H = 7.6 Hz, 1H, Ph), 7.69 (d, JH,H = 7.6 Hz, 2H, Ph),
7.76 (d, 3JH,H = 7.6 Hz, 2H, Ph). 19F NMR (CDCl3,
d
ppm): ꢀ81.2 (m,
2
3F, CF3), ꢀ113.0 (dm, JF,F = 293.3 Hz, 1F, CFAFB), ꢀ120.5 (dm,
(CDCl3, d ppm): 18.7 (s, CH3), 19.8 (s, CH3), 30.1 (s, SCH2), 33.3 (s,
2JF,F = 293.3 Hz, 1F, CFAFB), ꢀ125.8 (m, 2F, CF2). 13C NMR (CDCl3,
d
CH2), 67.1 (t, 2JC,F = 24.6 Hz, CCF2), 105.2 ꢀ118.0 (m, 6 ꢁ CF2), 130.1
ppm): 57.6 (dd, 2JC,F = 30.8 Hz, 2JC,F = 22.4 Hz, CH), 109.0–119.0 (m,
(s, Cq), 131.8 (s, Cq), 156.8 (t, JC,F = 26.6 Hz, C55O). MS: m/z = 470
2

S.S. Mykhaylychenko et al. / Journal of Fluorine Chemistry 140 (2012) 76–81
81
[Mꢀ1]. Anal. Calcd. for C14H13F12NOS: C, 35.7; H, 2.8; N, 3.0; S, 6.8.
Acknowledgement
Found: C, 35.6; H, 2.8; N, 2.8; S, 7.0.
We thank Dr. V. V. Trachevsky, Common Usage Centre of
Radiospectroscopy (Kiev), NAS of Ukraine, for recording the 13C
NMR spectra.
3.5.3. 2,2,3,3,4,4,5,5-Octafluoro-N-[2-(heptafluoropropyl)-4,5-
dimethyl-3,6-dihydro-2H-thiopyran-2-yl]pentanamide (11c)
Yield: 50%. Brown oil. 1H NMR (CDCl3,
d ppm): 1.74 (s, 6H,
2 ꢁ CH3), 2.78 (d, 2JH,H = 16.5 Hz, 1H, CHAHB), 3.15 (d,
References
2
2JH,H = 16.8 Hz, 1H, SCHAHB), 3.34 (d, JH,H = 16.5 Hz, 1H, CHAHB),
2
2
[1] (a) N.G. Zabirov, F.M. Shamsevaleev, R.A. Cherkasov, Russian Chemical Reviews
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3.69 (d, JH,H = 16.8 Hz, 1H, SCHAHB), 6.10 (tt, JH,F = 51.8 Hz,
3JH,F = 5.4 Hz, 1H, HCF2), 6.33 (bs, 1H, NH). 19F NMR (CDCl3,
d
(b) T.S. Jagodzinski, Chemical Reviews 103 (2003) 197–227;
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pounds 12 (2008) 1429–1459.
2
ppm): ꢀ82.1 (m, 3F, CF3), ꢀ115.5 (dm, JF,F = 279.1 Hz, 1F, CFAFB),
ꢀ117.2 (dm, 2JF,F = 279.1 Hz, 1F, CFAFB), ꢀ119.9 (dm,
2JF,F = 275.9 Hz, 1F, CFAFB), ꢀ121.6 (dm, 2JF,F = 275.9 Hz, 1F, CFAFB),
ꢀ124.0 (m, 2F, CF2), ꢀ126.4 (m, 2F, CF2), ꢀ130.0 (dm,
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(d) S.S. Mikhailichenko, A.V. Rudnichenko, V.M. Timoshenko, A.N. Chernega,
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(2011) 4788–4791.
2JF,F = 289.3 Hz, 1F, CFAFB), ꢀ131.9 (dm, 2JF,F = 289.3 Hz, 1F, CFAFB),
2
ꢀ138.7 (dm, JF,H = 51.8 Hz, 2F, HCF2). 13C NMR (CDCl3,
d ppm):
18.7 (s, CH3), 19.8 (s, CH3), 30.1 (s, SCH2), 33.1 (s, CH2), 67.8 (t,
2JC,F = 25.4 Hz, CCF2), 105.0–120.0 (m, CF3, 6 ꢁ CF2), 122.6 (s, Cq),
2
124.7 (s, Cq), 156.4 (t, JC,F = 26.0 Hz, C55O). MS: m/z = 538 [Mꢀ1].
Anal. Calcd. for C15H12F15NOS: C, 33.4; H, 2.2; N, 2.6; S, 6.0. Found:
C, 33.5; H, 2.3; N, 2.6; S, 6.2.
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946–947.
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(1985) 63–77.
3.5.4. N-[(2-Heptafluoropropyl)-4,5-dimethyl-3,6-dihydro-2H-
thiopyran-2-yl]-acetamide (11d)
Yield: 72%. Colorless solid. mp 120–122 8C. 1H NMR (CDCl3,
d
ppm): 1.75 (s, 3H, CH3), 1.78 (s, 3H, CH3), 1.98 (s, 3H, CH3CO) 2.63
(d, 2JH,H = 16.1 Hz, 1H, CHAHB), 3.09 (d, 2JH,H = 16.4 Hz, 1H, SCHAHB),
2
2
3.31 (d, JH,H = 16.1 Hz, 1H, CHAHB), 3.81 (d, JH,H = 16.4 Hz, 1H,
SCHAHB), 5.52 (bs, 1H, NH). 19F NMR (CDCl3,
d
ppm): ꢀ82.1 (m, 3F,
2
CF3), ꢀ114.6 (dm, JF,F = 276.6 Hz, 1F, CFAFB), ꢀ116.4 (dm,
2JF,F = 276.6 Hz, 1F, CFAFB), ꢀ123.0 (dm, 2JF,F = 287.1 Hz, 1F, CFAFB),
ꢀ125.3 (dm, JF,F = 287.1 Hz, 1F, CFAFB). 13C NMR (CDCl3,
d ppm):
2
18.8 (s, CH3), 19.8 (s, CH3), 24.4 (s, CH3CO), 30.4 (s, SCH2), 33.5 (s,
2
CH2), 67.7 (t, JC,F = 25.1 Hz, CCF2), 107.0–120.0 (m, CF3CF2CF2),
123.1 (s, Cq), 125.6 (s, Cq), 169.5 (s, C55O). MS: m/z = 354 [M+1].
Anal. Calcd. for C12H14F7NOS: C, 40.8; H, 4.0; N, 4.0; S, 9.1. Found: C,
40.9; H, 4.1; N, 3.9; S, 9.1.
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(2012) 6–21.