Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane with N-vinyl compounds

Article abstract of DOI:10.3762/bjoc.9.295

The reaction of hexafluorothioacetone dimer (2,2,4,4- tetrakis(trifluoromethyl)-1,3-dithiethane, 1) with vinylamides leads to the rapid formation of [2 + 2] cycloadducts: 4-amino-2,2-bis(trifluoromethyl) thietanes. The reaction proceeds in polar solvents (DMF, DMSO) in the absence of a catalyst at elevated temperature producing the corresponding cycloadducts in 47-86% yield. The reaction of N-vinylimidazole unexpectedly led to the formation of the corresponding 1-(hexafluoroisopropyl)-3-vinyl-1,3-dihydro-2Himidazole-2- thione (5). The structure of this compound, along with the structures of two new thietanes was confirmed by single crystal X-ray diffraction.

Full text of DOI:10.3762/bjoc.9.295

Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-
1,3-dithiethane with N-vinyl compounds
Viacheslav A. Petrov*1,§ and Will Marshall2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 2615–2619.
1DuPont Central Research and Development, Experimental Station,
PO Box 80500, Wilmington DE 19880-0500, USA and 2DuPont
Corporate Center for Analytical Sciences, Experimental Station, PO
Box 80500, Wilmington DE 19880-0500, USA
doi:10.3762/bjoc.9.295
Received: 04 September 2013
Accepted: 30 October 2013
Published: 21 November 2013
Email:
Viacheslav A. Petrov* - viacheslav.a.petrov@usa.dupont.com
This article is part of the Thematic Series "Organo-fluorine chemistry III".
Guest Editor: D. O'Hagan
* Corresponding author
§ Publication No 2013-877
© 2013 Petrov and Marshall; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
1-(hexafluoroisopropyl)-3-vinyl-1,3-dihydro-2H-imidazole-2-thione;
2,2,4,4-terakis(trifluoromethyl)-1,3-dithiethane;
4-amino-2,2-bis(trifluoromethyl)thietanes; organo-fluorine
Abstract
The reaction of hexafluorothioacetone dimer (2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane, 1) with vinylamides leads to the
rapid formation of [2 + 2] cycloadducts: 4-amino-2,2-bis(trifluoromethyl)thietanes. The reaction proceeds in polar solvents (DMF,
DMSO) in the absence of a catalyst at elevated temperature producing the corresponding cycloadducts in 47–86% yield. The reac-
tion of N-vinylimidazole unexpectedly led to the formation of the corresponding 1-(hexafluoroisopropyl)-3-vinyl-1,3-dihydro-2H-
imidazole-2-thione (5). The structure of this compound, along with the structures of two new thietanes was confirmed by single
crystal X-ray diffraction.
Introduction
Hexafluorothioacetone (HFTA) and hexafluorothioacetone very similar to the reactivity of HFTA) was reported to react
dimer (2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane (1) were with N-vinylcarbazole to give a [2 + 2] cycloadduct [10]. In this
shown to react with a wide variety of electron-rich olefins and paper we report the synthesis of 2,2-bis(trifluoromethyl)-4-
dienes, producing the corresponding cycloadducts. Reported amino-substituted thietanes by a reaction of 1 with selected
examples include the corresponding thietanes, derived from the vinylated amino compounds.
reaction of HFTA with vinyl ethers, vinyl sulfides, cyclic dienes
and styrenes [1,2], fluoride anion-catalyzed reactions of com- Results and Discussion
pound 1 with vinyl ethers [1,3,4], vinyl sulfides [3], ketene It was found that N-vinylamides 2a,b react with 1 in the
dimethylacetal [5], styrenes [6,7], cyclic dienes [8] and quadri- absence of a catalyst in polar solvents to produce the corres-
cyclane [9]. At this point, no data for the reaction of HFTA or ponding thietanes 3a,b in moderate yield (Scheme 1). The reac-
HFTA dimer with vinylamines can be found in the literature, tion can be carried out at either ambient or elevated tempera-
despite the fact that (CF3)2C=C=S (which exhibits a reactivity ture (see Table 1).
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Table 1: Reaction conditions, yields, melting/boiling points and MS data for compounds 3a–e and 5.
Compound
Methoda Temp. (°C)/Time (h), Solvent
Yield (%)
Mp (°C), (bp °C/mmHg)
MS (m/z)
3a
3b
A
A
25/72, DMF
25/16, DMSO
47
75c
orange oilb
93–94
253 (M+, C6H5F6NOS+)
281 (M+, C8H9F6NOS+)
A
A
B
70/14, DMF
70/16, neatd
25–50/12, DMF
48
69
56
3c
3d
3e
A
A
70–80/2, DMF
70/24, DMF
86
81–82
293 (M+, C9H9F6NOS+)
321 (M+, C11H13F6NOS+)
375 (C17H11F6NS+)
55–86
80–81
A
B
70/2, DMF
25/16, DMF
55
60
103–103.5
5
A
A
25/48, DMF
70/2, DMF
50
48
40–41 (74/2)
276 (M+, C8H6F6N2S+)
aMethod A: no catalyst; method B: HFP, Sx, DMF, one-pot reaction. bPurity 98%, GC–MS, NMR. c90% by NMR. dThree molar excess of vinylamide
was used.
Interestingly, the 19F and 1H NMR spectra of both compounds
3a and 3b show two sets of signals, probably being a result of
restricted rotation around the C–N bond in the amide fragment,
similar to restricted rotation of –N(CH3)2 in dimethylform-
amide. Cyclic lactames 2c,d bearing a vinyl group at the
nitrogen also undergo reaction with 1 producing the corres-
ponding thietanes 3c,d (Scheme 2).
Scheme 1: Reaction of vinylamides 2a,b with 1.
It should be pointed out that in case of compound 2b the reac-
tion can be performed in an excess of vinylamine as the solvent.
The reaction is highly selective (NMR), leading to the exclu-
sive formation of thietanes and fluctuations in the isolated
yields of compounds 3a and 3b are connected to the isolation
protocol (see Experimental). In contrast to the corresponding
cycloadducts of vinyl ethers and HFTA (2,2-bis(trifluo-
Scheme 2: Reaction of N-vinyllactames 2c,d with 1.
romethyl)-4-alkoxythietanes), which are high-boiling liquids
[3], thietanes 3a and 3b are solids at room temperature. The
structure of purified 3b was established by single crystal X-ray
It should be pointed out that in sharp contrast to compounds
3a,b, NMR spectra of 3c and 3d exhibit only one set of signals,
which might be indicative of a significantly lower rotation
barrier around the C–N bond in these two materials. The struc-
tures of both 3c and 3d were established by single crystal X-ray
diffraction. Compounds 3b and 3e were also prepared in
56–60% yield by using a one-step process in which dimer 1 was
generated by the reaction of hexafluoropropene (HFP) with
sulfur in the presence of CsF as catalyst, followed by the addi-
tion of vinyl compounds 2b or 2e without the isolation of
dimer 1.
diffraction (Figure 1).
N-vinylcarbazole (2e) was found to have the highest reactivity
towards 1. Indeed, when the mixture of 2e and 1 in DMF was
heated at 70 °C, no starting carbazole was found in the reaction
Figure 1: Crystal structure of 3b with thermal ellipsoids drawn at the
30% probability level.
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Beilstein J. Org. Chem. 2013, 9, 2615–2619.
mixture after 2 hours (NMR). This reaction led to the selective
formation of thietane 3e, isolated in 67% yield (Scheme 3). The
structure of 3e was established by single crystal X-ray diffrac-
tion (Figure 2).
Scheme 4: Formation of thione 5 in reaction of 4 and 1.
Scheme 3: Reaction of N-vinylcarbazole with 1.
Figure 3: Crystal structure of 5 with thermal ellipsoids drawn at the
30% probability level.
towards dimer 1 and even after prolonged heating (70 °C, 48 h,
DMF) only starting materials were observed in the reaction
mixture (NMR).
The mechanistic aspect of thione 5 formation is not clear at this
point. The formation of the corresponding thiones in the reac-
tion of 1 with N-alkylimidazoles was found to be common in
nature.
Experimental
1H NMR and 19F NMR spectra were recorded on a Bruker
DRX-500 (499.87 MHz) instrument by using CFCl3 or TMS as
an internal standard. CDCl3 was used as a lock solvent. GC and
GC–MS analyses were carried out on a HP-6890 instrument by
Figure 2: Crystal structure of 3e with thermal ellipsoids drawn at the
30% probability level. Disordered atoms are omitted for clarity.
Interestingly, the 19F and 1H NMR spectra of 3e showed only using an HP FFAP capillary column and either TCD (GC) or
one set of signals, despite the fact that in the corresponding mass-selective (GC–MS) detectors, respectively. Dry DMF
cyclopropane (prepared by the reaction of compound 3e with (water <100 ppm), vinylamines 2a–e and 4 (Aldrich), sulfur
PBu3), restricted rotation around the C–N bond was observed (Alfa Aesar, sublimed, 99.5%, 100 mesh) and hexafluoro-
[11].
propene (DuPont) were purchased and used without further
purification. CsF (Aldrich, 99%) was dried at 100–120 °C under
N-vinylimidazole (4) was found to have a different reactivity dynamic vacuum and stored and handled inside of glove box.
profile. The reaction of 4 with 1 (25 °C, 48 h) unexpectedly led
to the formation of thione 5 (rather than the corresponding Compound 1 (liquid, purity 93–98%) was prepared by using
thietane) as a sole product (NMR, Scheme 4). Thione 5 was modified literature procedure reported in [12] and was used
isolated in 48–50% yield and its structure was established by without further purification.
single crystal X-ray diffraction (Figure 3).
Due to the high ratio of sulfur to fluorine, the elemental analysis
At elevated temperature, the reaction of 4 with 1 was signifi- of new materials was not attempted. The purity of all new com-
cantly faster and it was completed after 2 h at 70 °C in DMF. pounds established by GC and NMR spectroscopy was at least
On the other hand, N-vinyl-1,3,4-triazole was found to be inert 98%.
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Beilstein J. Org. Chem. 2013, 9, 2615–2619.
Crystallography
under reduced pressure and the residue was purified either by
X-ray data for 3b, 3e and 5a were collected at −100 °C by using crystallization from hexane or distillation (compound 5).
a Bruker 1K CCD system equipped with a sealed tube molyb-
denum source and a graphite monochromator. The structures Method B: Inside a glove box a dry three-necked round-
were solved and refined with the Shelxtl [13] software package, bottomed flask was charged with 0.5–1.0 g of dry CsF. The
refinement by full-matrix least squares on F2, scattering factors flask was taken out and equipped with dry-ice condenser, ther-
from Int. Tab. Vol. C Tables 4.2.6.8 and 6.1.1.4. Crystallo- mocouple, gas inlet tube and 100 mL of dry DMF was added by
graphic data (excluding structure factors) for the structures in using a syringe, followed by the addition of 6.4 g (0.2 mol) of
this paper have been deposited with the Cambridge Crystallo- sublimed sulfur. The reaction mixture was agitated for
graphic Data Centre as supplementary publication nos. CCDC 15–20 min, while the temperature was raised up to 35–40 °C.
#956557-956559. Copies of the data can be obtained, free of This process was accompanied by the development of a dark
charge, on application to CCDC, 12 Union Road, Cambridge blue–brown color of the reaction mixture. Hexafluoropropene
CB2 1EZ, UK, (fax: +44 1223 336033 or e-mail: 32 g (0.21 mol) was added as a gas to the reaction mixture, and
deposit@ccdc.cam.ac.uk).
the temperature usually rose to 65–70 °C during the addition
and at the end all sulfur went into solution. The reaction mix-
ture was cooled to an ambient temperature followed by the ad-
dition of the corresponding N-vinyl compound, and the reaction
Reaction of 1 with 2a–e and 4 (typical
procedure)
Method A: To a solution of the corresponding vinyl compound mixture was agitated for 12–16 h. Afterwards the mixture was
(0.01–0.02 mol) in 15 mL of solvent was added 0.005–0.01 mol diluted with water (500 mL) and extracted with hexane
of dimer 1. The reaction mixture was agitated for 2–72 h at (3 × 100 mL). The combined organic layers were washed with
either ambient or elevated temperature. The reaction mixture water (3 × 200 mL) and dried over MgSO4. The solvent was
was diluted by water (300 mL, extracted with hexane removed under reduced pressure, and the residue was purified
(3 × 50 mL). Combined organic layers were washed by water either by crystallization from hexane or distillation (see Table 1
(3 × 200 mL) and dried over MgSO4. The solvent was removed for conditions and yields and Table 2 for NMR data).
Table 2: 1H, 19F, 13C NMR data for compounds 3a–e and 5.
Entry Compound 1H NMRa
(δ, ppm, J, Hz)
19F NMRa
(δ, ppm, J, Hz)
13C NMRa,b
(δ, ppm, J, Hz)
1
3a c
Major: 3.03 (1H, m), 3.55 (1H, m), 5.82 Major: −73.80 (s)d
Major: 38.4, 41.2, 46.6 (sept., 32.0),
(1H, dd, 7.8), 6.40 (1H, br.s), 8.18 (1H,
s)
123.3 (q, 278.0), 124.2 (q, 276.0), 161.3
Minor: 3.21 (1H, dd), 3.51 (1H, dd), 5.35 Minor: −73.65 (m),
(1H, m), 6.39 (br. s), 8.13 (1H, d, 11.0)
−73.59 (m)
2
3be
Major: 3.13 (3H, s), 2.19 (3H, s), 3.15
(1H, m), 3.32 (1H, m), 6.67 (1H, t, 7.8)
Major: −72.73 (3F, q,
9.6), −73.78 (3F, q,
9.6)
Major: 22.51, 29.6, 34.5, 45.8 (sept.,
31.8), 47.5, 123.5 (q, 280), 124.4 (q,
284), 171.8
Minor: 2.17 (s), 3.59 (s), 5.89 (m)
Minor: −72.66 (br.s),
−73.78
3
4
5
6
3c
3d
3e
5
2.11 (2H, sept, 7.0), 2.44 (2H, m), 3.25 −73.09 (3F, q, 9.6),
17.5, 31.3, 34.5, 41.9, 45.2, 45.8 (sept,
33.1), 123.4 (q, 279), 124.5 (q, 279),
175.6
(1H, dd), 3.37 (1H, dd), 3.60 (1H, m),
3.85 (1H, m), 6.16 (1H, t, 8.0)
−73.91 (3F, q, 9.6)
1.68 (3H, m), 1.76 (3H, m), 2.56 (1H, t, −72.63 (3F, q, 10.3),
23.23, 29.5, 29.6, 35.7, 37.4, 42.7, 46.0
(sept,. 31.9), 47.4, 123.4 (q, 277), 124.6
(q, 279), 176.5
8.1), 3.21 (2H, m), 3.70 (2H, m), 6.63
(1H, t, 8.1)
−73.70 (3F, q, 10.3)
3.45 (1H, m), 4.50 (1H, m), 6.75 (1H, t), −70.81 (3F, q, 8.0),
38.2, 46.9 (sept, 32.0), 48.9, 110.6 (q,
1.5), 120.6, 121.2, 123.5 (q, 281),
124.5, 126.3, 130.3
7.33 (2H, m), 7.50 (2H, m), 7.54 (2H,
m), 7.92 (2H, m)
−73.22 (3F, q, 8.0)
5.06 (1H, dd, 8.8, 2.0), 5.25 (1H, dd,
16.3, 2.5), 6.72 (sept, 7.1), 6.99 (1H,s),
7.06 (1H, d, 2.5), 7.50 (1H, dd 16.3, 8.8)
−69.19 (d, 7.1)
aIn CDCl3 as lock solvent. b{H}C13 NMR spectra. cTwo partially overlapped sets of signals, ratio 5:1. d19F NMR of 3a in the presence of DMF (CDCl3):
Major: −73.58 (3F, q, 10.1 Hz), −73.94 (3F, q, 10.1 Hz) ppm; minor: −73.24 (3F, q, 10.1 Hz), −73.75 (3F, q, 10.1 Hz) ppm. eTwo partially overlapped
sets of signals, ratio 3:1.
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Acknowledgements
The authors are grateful to Dr. Chris Junk for helpful discus-
sions, the reviewers for valuable suggestions, and Timothy
Bentz for technical support.
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