Unusual reactivity of 3-chloro-1-pentafluorosulfanylpropene in nucleophilic substitution reactions

Article abstract of DOI:10.1016/j.tetlet.2005.05.041

Treatment of 3-chloro-1-pentafluorosulfanylprop-1-ene 1 with KCN yielded the product of prototropic rearrangement ClCHCHCH₂SF₅, whereas reactions with NaN₃ and KSCN gave the S_N2 products. Ab initio calculations

Full text of DOI:10.1016/j.tetlet.2005.05.041

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4777–4779
Unusual reactivity of 3-chloro-1-pentafluorosulfanylpropene
in nucleophilic substitution reactions
Igor V. Trushkova and Valery K. Brelb,*
aMoscow State University, Department of Chemistry, Leninskie Gory, 1/3, Moscow 119992, Russian Federation
bInstitute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation
Received 6 March 2005; revised 1 May 2005; accepted 11 May 2005
Available online 31 May 2005
Abstract—Treatment of 3-chloro-1-pentafluorosulfanylprop-1-ene 1 with KCN yielded the product of prototropic rearrangement
ClCH@CHCH2SF5, whereas reactions with NaN3 and KSCN gave the SN2 products. Ab initio calculations at MP2/6-
311++G** level are used to explain the unusual behaviour of cyanide. It was found that proton transfers from both 1 to CNꢀ
and from HCN to the anion of 1 are exothermic. In contrast, azide and thiocyanate ions are too weakly basic to deprotonate 1.
Ó 2005 Elsevier Ltd. All rights reserved.
The introduction of a pentafluorosulfanyl group, SF5,
into organic molecules brings about substantial changes
with regard to their physical, chemical and biological
behaviour. Compounds containing this group often
possess advantageous properties due to the electronega-
tivity, high hydrolytic stability and steric effect of the
SF5-substituent. These properties are manifested in
various potential applications such as solvents for poly-
mers, surfactants, fumigants, rocket fuels and others.1–4
Therefore, the preparation of new organic molecules
with an SF5-group as well as the investigation of their
properties, is very important for both theoretical and
applied chemistry.
sequence (Scheme 1). The pentafluorosulfanyl group
was introduced into allyl alcohol 2 by gas-phase radical
addition of F5SCl and subsequent alkali treatment, fol-
lowing a known method of synthesis of pentafluorosul-
fanylethene.5 Standard treatment of the resulting
alcohol 4 with thionyl chloride gave the corresponding
allyl chloride 1.
With the intention of preparing some heteroaromatic
compounds containing the F5S-moiety (thiazoles, triaz-
oles, tetrazoles, etc.), we studied the reactions of 1 with
different nucleophiles. It was found that this substrate
reacted smoothly at 40–50 °C with sodium azide yielding
5, the product of nucleophilic substitution in ca. 83%
yield. Similarly, treatment with potassium thiocyanate
gave rise to the corresponding product of SN2 reaction
(Scheme 2).
Allylic systems have a broad scope in organic synthesis
due to their high reactivity and ability to form different
kinds of products with or without allylic rearrangement
depending on their structure, the nature of reagent and
reaction conditions. In the course of our investigations
of the synthesis and reactivity of pentafluorosulfanyl-
containing organic compounds, we synthesized 3-
chloro-1-pentafluorosulfanylpropene 1 by a three-step
However, reaction of 1 with KCN failed to give the
nucleophilic substitution product. Instead of the nitrile,
we isolated 1-chloro-3-pentafluorosulfanylpropene 7
(Scheme 3).
KOH
F5SCl
SOCl2, Py
OH
F5S
OH
F5S
F5S
OH
Cl
30 ˚C,
yield 67%
yield 73%
hν, r.t.,
yield 94%
Cl
2
1
4
3
Scheme 1.
Keywords: Pentafluorosulfanyl group; Nucleophilic substitution; Rearrangements.
*
Corresponding author. Tel./fax: +7 095 785 7024; e-mail: brel@ipac.ac.ru
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.041

4778
I. V. Trushkov, V. K. Brel / Tetrahedron Letters 46 (2005) 4777–4779
NaN3
KSCN
F5S
N3
N
F5S
SC
F5S
Cl
MeOH,
40-50 ˚C,
yield 83%
MeOH,
40-50˚C,
yield 75%
5
1
6
Scheme 2.
KCN
KCN
Cl
F5S
F5S
CN
F5S
Cl
MeOH, r.t.,
yield 78%
MeOH
7
1
Scheme 3.
R
R'
R
R'
-
R'
-
R
CN
NC
Cl
R
CN
R
Cl
NC
R'
Cl
NC
H R'
Scheme 4.
This result was unexpected since allyl chlorides are nor-
mally very good substrates for nucleophilic substitution
reactions. We have found a single example of a similar
nucleophile-induced double bond migration in substi-
tuted allyl chlorides: treatment of 3-chloro-3-(4-nitro-
phenyl)propene with triethylamine gave rise to the
corresponding styrene derivative.6 Moreover, cyanide
is usually considered to be a good nucleophile with rel-
atively low basicity.7 Therefore, SN2 or SN20 reactions
are expected between cyanide and allylic substrates
(Scheme 4).
we showed9 that the basicity of the nucleophile is an
important factor in SN2/SN20 competition: the higher
the basicity of the nucleophile, the more preferable is at-
tack on the c carbon atom. Electron-withdrawing
groups in the substrate also favour the SN20 mechanism.
This is why the energy barrier for the SN2 reaction of a
cyanide ion with 1 is large. At the same time, steric ef-
fects prevent SN20 reaction. However, the basicity of
cyanide also has another effect: cyanide can deprotonate
an appropriate substrate. The base-catalyzed nature of
isomerization of 1–7 is supported by the fact that treat-
ment of 1 with the slightly more basic potassium carbon-
ate leads to the same result.
We have calculated8 the structure and properties of 1 to
understand the effect of the SF5-substituent on the
chemical behaviour of the allyl chloride (Table 1). The
results obtained showed that a charge-controlled reac-
tion would proceed on an a carbon atom but orbital
control moves the nucleophilic attack to the c carbon.
However, the bulkiness of the pentafluorosulfanyl group
prevents an SN20 reaction. As a result, even soft nucleo-
philes react with 1 by an SN2 mechanism. All three stud-
ied anions (N3ꢀ, SCNꢀ, CNꢀ) are good nucleophiles but
weak bases.7 Cyanide is the most basic of them. Earlier,
Proton transfer is a fast process for exothermic reactions
between O-, N- and S-atoms but is relatively slow for
CH-acids. This has been explained by non-perfect syn-
chronization between the extent of proton transfer and
the extent of delocalization of a negative charge in the
developing carbanion.10 The more efficient is the meso-
meric stabilization of the carbanion, the slower is proton
transfer from a CH-acid with the same acidity. However,
the electron-withdrawing effect exerted by the penta-
fluorosulfanyl group is believed to be inductive rather
than a mesomeric effect. Therefore, proton transfer from
1 must be fast for an exothermic process. We have calcu-
lated the reaction energy for the deprotonation of 1 by
different anions as well as for the overall transformation
of 1 into 7 (Table 2). The isomerization process is exo-
Table 1. The contributions of a and c carbon atoms of 1 to LUMO, n,
and charges on atom, Q, calculated at MP2/6-311G** levels
nCa
nCc
QCa
QCc
QCH2
QCH
ꢀ0.12
0.18
0.42
ꢀ0.20
ꢀ0.31
0.13
Table 2. Reaction energies for processes 1 + Nuꢀ ¡ 8 + HNu and 8 + HNu ¡ 2 + Nuꢀ calculated at MP2/6-311++G** level, kcal/mol
-
-
F5S
Cl
Nu
+
-
HNu
+
F5S
Cl
F5S
Cl
Nu
+
1
8
2
Nu
1 + Nuꢀ ¡ 8 + HNu
8 + HNu ¡ 2 + Nuꢀ
CNꢀ
ꢀ2.9
11.0
32.6
ꢀ1.4
ꢀ15.3
ꢀ36.9
ꢀ
N3
SCNꢀ

I. V. Trushkov, V. K. Brel / Tetrahedron Letters 46 (2005) 4777–4779
4779
8. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G.
E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.;
Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.;
Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko,
A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R.
L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J.
L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.;
Pople, J. A. Gaussian 98, Revision A.7; Gaussian: Pitts-
burgh, PA, 1998.
9. Trushkov, I. V. Presented at the XIV International
Conference on Physical Organic Chemistry, Florianopolis,
Brazil, 1998.
10. Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301–308.
11. Compound 1: liquid, bp 64–65 °C (60 mm). 1H NMR
(200 MHz, CDCl3): d = 4.18–4.21 (m, 2H), 6.51–6.86 (m,
2H); 13C NMR (50.3 MHz, CDCl3): d = 40.95 (s), 133.0
thermic: calculations by HF/6-31G, MP2/6-311G** and
MP2/6-311++G** gave reaction energies of ꢀ5.5, ꢀ3.8
and ꢀ4.3 kcal/mol, respectively. The data in Table 2
demonstrates that both azide and thiocyanate ions are
too weak to deprotonate 1 or 7. In the case of cyanide,
both deprotonation of 1 and reprotonation of the allyl
anion 8 leading to 7 are exothermic processes. The low
reactivity of 1 in nucleophilic substitution reactions, ex-
plains the unusual behaviour of cyanide but ÔnormalÕ
reactivity of azide and thiocyanate ions. In the case of
cyanide, the exothermic proton transfer predominates.
Deprotonation is impossible for azide and thiocyanate
ions due to high endothermicity. So, for azide and thio-
cyanate, an SN2 reaction is the only possible process.
It was found that N3ꢀ and SCNꢀ react with 3-chloro-1-
pentafluorosulfanylprop-1-ene by SN2 reaction but
treatment of this substrate with CNꢀ leads to 1-
chloro-3-pentafluorosulfanylprop-1-ene by base-cata-
lyzed double bond migration. These results have been
interpreted using ab initio calculations at the MP2/6-
311++G** level. It was shown that proton transfer from
1 to a cyanide ion is an exothermic process, in contrast
to the other studied nucleophiles. At the same time, 1 is
an unreactive substrate in SN20 processes and has low
reactivity in SN2 reactions. The structures of 1, 4–7 were
(pent, JC–F = 7.4 Hz), 143.55 (d pent, JC–F = 1.6 Hz, JC–F
=
21.3 Hz); 19F NMR (188 MHz, CDCl3): d = 140.56 (m,
incl. app. d, JF–F = 148.0 Hz, 4F), 157.67–160.86 (m, 1F).
Elemental analysis: % calcd for C3H4ClF5S: C, 17.79; H,
1.99; S, 15.83%; found: C, 17.94; H, 2.07; S, 15.67%.
Compound 4: liquid, bp 83 °C (20 mm). 1H NMR (200
MHz, CDCl3): d = 4.26 (t, br, JH–H = 5.6 Hz, 1H), 4.31–
4.41 (m, 2H), 6.53–6.83 (m, 2H); 13C NMR (50.3 MHz,
CDCl3): d = 59.97 (s), 137.36 (pent, JC–F = 7.0 Hz), 140.22
(d pent, JC–F = 1.7 Hz, JC–F = 20.7 Hz); 19F NMR (188
MHz, CDCl3): d = 141.30 (m, incl. app. d, JF–F = 150.9 Hz,
4F), 159.68–162.88 (m, 1F). Elemental analysis: % calcd for
C3H5F5OS: C, 19.57; H, 2.74; S, 17.40%; found: C, 19.42;
H, 2.82; S, 17.57%. Compound 5: oil. 1H NMR (200 MHz,
CDCl3): d = 4.09 (d pent, JH–H = 2.4 Hz, JH–H = 2.0 Hz,
2H), 6.47–6.59 (m, 1H), 6.74 (d pent t, JH–H = 8.4 Hz,
JH–F = 6.2 Hz, JH–H = 1.8 Hz, 1H); 13C NMR (50.3 MHz,
CDCl3): d = 49.97 (s), 132.71 (pent, JC–F = 7.1 Hz), 142.90
(d pent, JC–F = 1.7 Hz, JC–F = 21.3 Hz); 19F NMR (188
MHz, CDCl3): d = 140.39 (m, incl. app. d, JF–F = 150.5 Hz,
4F), 157.94–161.13 (m, 1F). Elemental analysis: % calcd for
C3H4F5N3S: C, 17.23; H, 1.93; S, 15.32%; found: C, 17.48;
H, 2.12; S, 15.60%. Compound 6: oil. 1H NMR (200 MHz,
CDCl3): d = 3.65–3.66 (m, 1H), 3.67–3.69 (m, 1H), 6.54–
6.86 (m, 2H); 13C NMR (50.3 MHz, CDCl3): d = 33.24 (s),
110.49 (s), 131.41 (pent, JC–F = 7.0 Hz), 145.12 (d pent,
JC–F = 1.5 Hz, JC–F = 20.1 Hz); 19F NMR (188 MHz,
CDCl3): d = 140.51 (m, incl. app. d, JF–F = 150.4 Hz, 4F),
156.61–159.81 (m, 1F). Elemental analysis: % calcd for
C4H4F5NS2: C, 21.33; H, 1.79; S, 28.48%; found: C, 21.47;
H, 1.84; S, 28.56%. Compound 7: liquid, bp 72 °C (65 mm).
1
13
proved by H, 19F and C NMR spectroscopy.11
Acknowledgements
This work was supported by grants from the European
Office of Aerospace Research and Development
(EOARD # 037004) and the International Science and
Technology Center (ISTC # 2791).
References and notes
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352–374.
1H NMR (200 MHz, CDCl3): d = 4.55 (dd pent, JH–H
7.2 Hz, JH–H = 0.5 Hz, JH–F = 7.6 Hz, 2H), 6.12 (dd,
JH–H = 7.2 Hz, JH–H = 7.6 Hz, 1H), 6.50 (dt, JH–H
=
3. Bovin, J. L. Can. Patent 1,085,875, 1980.
4. Sitzmann, M. E. J. Fluorine Chem. 1995, 70, 31–38.
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1961, 2066–2070.
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Chemistry. Reactions, Mechanisms, and Structure, 5th
ed.; Wiley, 2000, 2083 pp.
=
7.2 Hz, JH–H = 1.0 Hz, 1H); 13C NMR (50.3 MHz, CDCl3):
d = 67.05 (dt pent, JC–F = 1.0 Hz, JC–F = 16.5 Hz), 120.91
(pent, JC–F = 4.1 Hz), 126.58 (pent, JC–F = 1.0 Hz); 19F
NMR (188 MHz, CDCl3): d = 143.72 (m, incl. app. d,
JF–F = 145.0 Hz, 4F), 157.50–161.23 (m, 1F). Elemental
analysis: % calcd for C3H4ClF5S: C, 17.79; H, 1.99; S,
15.83%; found: C, 17.84; H, 2.05; S, 15.97%.