Preparation of (perfluoroalkyl)alkane thiols via Zemplén deacylation of fluorous (perfluoroalkyl)alkyl thioacetates

Article abstract of DOI:10.1016/j.jfluchem.2018.02.014

Convenient and robust synthesis of (perfluoroalkyl)alkane thiols [(C_nF_2n+1(CH₂)_mSH); m/n = 3/4,6,8,10, 4a-d; m/n = 2/6, 8; m/n = 1/1,2,3,7,8H, 12a-e] was developed starting from commercially available fluorous alcohols (1a-d, 5, 9a-e). The intermediate (perfluoroalkyl)alkyl iodides and/or sulfonates were reacted with potassium thioacetate in DMF, and the resulting thioacetates were deacetylated by a Zemplén analogue reaction. The (perfluoroalkyl)alkane thiols were obtained in good overall yields and high purity.

Full text of DOI:10.1016/j.jfluchem.2018.02.014

Accepted Manuscript
´
Title: PREPARATION OF (PERFLUOROALKYL)ALKANE THIOLS VIA ZEMPLEN
DEACYLATION OF FLUOROUS (PERFLUOROALKYL)ALKYL THIOACETATES
´
´
´ ´ ´
Authors: Balint Menczinger, Aniko Nemes, Csongor Szıjjarto,
´
´
Jozsef Rabai
PII:
S0022-1139(18)30063-0
DOI:
Reference:
https://doi.org/10.1016/j.jfluchem.2018.02.014
FLUOR 9128
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Received date:
Revised date:
Accepted date:
7-2-2018
26-2-2018
26-2-2018
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Please cite this article as: Menczinger B, Nemes A, Szıjjarto C, Rabai J, <ce:small-
´
caps>Preparation of (Perfluoroalkyl)alkane Thiols via Zemplen Deacylation of
Fluorous (Perfluoroalkyl)alkyl Thioacetates</ce:small-caps>, Journal of Fluorine
Chemistry (2010), https://doi.org/10.1016/j.jfluchem.2018.02.014
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PREPARATION OF (PERFLUOROALKYL)ALKANE THIOLS VIA ZEMPLÉN DEACYLATION OF
FLUOROUS (PERFLUOROALKYL)ALKYL THIOACETATES
Bálint Menczinger, Anikó Nemes, Csongor Szíjjártó, József Rábai*
Eötvös Loránd University, Institute of Chemistry, Pázmány Péter sétány 1/A, 1117
Budapest, Hungary
Dedicated to the memory of Prof. George Olah
Graphical abstract
Highlights



Adaption of Zemplén deacylation for thioacetares
Effective stochiometric synthesis of thioacetates from iodides and/or sulfonates
Pure perfluoroalkyl thioacetates and thiols are accessible without chromatography
Abstract
1

Convenient and robust synthesis of (perfluoroalkyl)alkane thiols [(CnF2n+1(CH2)mSH);
m/n = 3/4,6,8,10, 4a-d; m/n = 2/6, 8; m/n = 1/1,2,3,7,8H, 12a-e] was developed starting
from commercially available fluorous alcohols (1a-d, 5, 9a-e). The intermediate
(perfluoroalkyl)alkyl iodides and/or sulfonates were reacted with potassium thioacetate
in DMF, and the resulting thioacetates were deacetylated by a Zemplén analogue
reaction. The (perfluoroalkyl)alkane thiols were obtained in good overall yields and
high purity.
1. Introduction
Fluorous chemistry [1] now seems to match with one of the visions of Joseph Simons
as he disclosed in his 1973 ACS award lecture: “The seventh age of Fluorine
Chemistry or perhaps its seventh heaven, is the age of the future. (…) The new
reactions will not be restricted to those of fluorocarbons with fluorocarbons, they will
include reactions of fluorocarbons with organic molecules or other kinds of molecules
to produce substances part fluorocarbon and part something else” [2].
(Perfluoroalkyl)alkane thiols (CnF2n+1(CH2)mSH) are classified as fluorous compounds,
and are also named as hemifluorinated alkyl mercaptanes. Their chemical reactivity
and physico-chemical properties can be tuned by their molecular structure, i.e. with
the ratio of the fluorocarbon and hydrocarbon segments (n/m).
The title organosulfur compounds play important role in diverse areas of chemistry,
including biochemistry, fluorous synthesis, materials science, and technology.
Fluorous analogs of metalloenzyme cofactors with four iron-four sulfur clusters were
synthesized and studied recently [3]. Fluorous thioglycosyl donors showed good
performance in oligosaccharide synthesis [4]. Fluorous thiols, e.g. C8F17CH2CH2SH,
have been applied as nucleophilic scavengers, fluorous tags for heterocycles, and
precursors for synthesis of fluorous sulfides [5]. Some fluorous and consequently
2

relatively volatile porphyrins [e.g. meso-(p-C8F17CH2CH2SC6F4)4porH2] showed
quantum interferences in molecule interferometry experiments [6].
Air/water bubble stabilization was effected with C6F13CH2CH2(OCH2CH2)4SH type
perfluoroalkylated poly(oxyethylene) thiol amphiphiles [7]. Since thiols also form
relatively strong bonds with metal or metal oxide surfaces, they are used in materials
science as self-assembling monolayers (SAMs) for surface modification. Partially
fluorinated thiols (CnF2n+1(CH2)mSH, n = 6–10; m = 2–17) were also synthesized, which
produced nanocoatings on gold surfaces with controlled wettability [8]. The study of
such fluorous SAMs has become intensive [9]. F-thiols are used for corrosion
prevention [10] and for making superhydrophobic surfaces and/or functional surfaces
of medical implants [11]. Stable spherical nanospheres of average 260 nm size were
obtained in water from perfluorohexyl- and perfluorooctyl-propanethio-β-
cyclodextrines [12]. Fluorocarbon soluble nanocrystals, nanorods, nanotubes and gold
nanoparticles were prepared using fluorous thiols (n = 8/6, m = 3/2; [13]). Pristine
quality semifluorinated monolayers on gold were prepared using high purity
(perfluoroalkyl)alkyl thioacetate precursors [14]. Membrane protein isolations were
performed without denaturation using F-amphiphiles prepared from hemifluorinated
thiols and S-alkylating reagents having glycosylic units [15].
Fluorous thiols with different n/m ratio (m ≥ 2) are prepared using methods known for
the introduction of the thiol functional group into the hydrocarbon analogues [16], or by
the introduction of perfluoroalkyl groups into appropriately protected thiol derivatives
with terminal olefin bonds [17]. The former ones frequently include H2S [18]; thiolacetic
acid [19] and/or their salts [20], thiourea [19, 21], and thiosulfate [19] as sulfur transfer
reagents. In many cases, however, the latter reagents are used in large excess in
comparison to (perfluoroalkyl)alkylating reagents, most frequently sulfonate esters
[22].
3

The synthesis of fluorous thiols (m ≥ 2) is usually accomplished through a thioacetate
intermediate, which then is converted to the appropriate thiol by reduction with LiAlH4
in THF [8b, 19b] or with NaBH4 in methanol [15]. Deprotection of such thiolesters can
alternatively be performed by solvolysis with methanol, assisted by in situ generated
hydrochloric acid [7], or using an excess of base (NaOCH3/CH3OH; NH3 pressure) [23].
The latter ammonolysis method involves the easy phase separation of the liquid thiols
and the solid side product acetamide.
The present study is related to the optimization of the synthesis of fluorous
thioacetates, alkanethiols and that of the product isolation protocols based on the
experimental observation of the phase preference and/or volatility of the fluorous
products formed.
2. Results and Discussion
Our syntheses involved fluorinated primary alcohols 1, 5 and 9 as precursors, which
were first converted to the appropriate alkylating reagents 2, 8, and 10. Since their
reactivity is highly affected with the number of methylene groups (m) between the
electron withdrawing perfluoroalkyl- and the leaving groups [24], (perfluoroalkyl)propyl
iodides (m = 3, 2a-d) [25], (perfluorohexyl)ethyl tosylate (m = 2, 5), and
(perfluoroalkyl)methyl (m = 1) nonaflates (10a-c) or -triflates (10d-e) were selected and
prepared [26] similarly to literature examples [27]. The reactivity of 3-
(perfluoroalkyl)propyl iodides (2a-d) in nucleophilic substitution reactions are
comparable with the non-fluorinated compounds. It is worthy to note, that the 3-
(perfluoroalkyl)propyl iodides (2a-d) are prepared from the appropriate fluorous
alcohol with in situ generated PI3 using red phosphorus and iodine [25]. 2-
(Perfluoroalkyl)ethyl derivative (m = 2, 6) reacts with nucleophiles under similar
reaction conditions. The replacement of tosylate 6 with the industrial telomer iodide,
C6F13CH2CH2I, (Scheme 1, not shown) gave similarly good yield of thiolester 7
(Experimental). In the case of 1H,1H-perfluoroalkyl tosylates the negative inductive
4

effect of the perfluoroalkyl moiety cause dramatic decrease in the reactivity towards
nucleophiles. This effect can be overwhelmed by strong electron withdrawing R` (CF3
or C4F9) groups of the sulfonate ester moiety, thus trifluoromethanesulfonates and
nonafluorobutanesulfonates were applied as leaving groups in the case of m = 1 (10a-
c, 10d-e). These active esters were synthesized in good yield from the fluorous
alcohols with trifluoromethanesulfonyl anhydride or nonafluorobutanesulfonyl fluoride
in the presence of base [cf. Ref. 27]. The above mentioned sulfonyl fluoride reagent
was used in the case of 10a-c (n = 1, 2, 3) to prevent the formation of very volatile
sulfonate intermediates (Scheme 1). The atmospheric boiling points of the above
nonaflates were determined, and they showed higher figures than the corresponding
triflates (Table 1), as expected [28].
In the next reaction, the above fluoroalkylation reagents were reacted with a slight
excess of potassium thioacetate in DMF solution to afford the appropriate thiolesters
3, 7, and 11 in good to excellent yield. While this reaction takes place during 2h at
room temperature with triflates and nonaflates (10a-c), in the case of iodides (2a-d)
and tosylate (6) stirring at 80oC for 0.5-2h, respectively, was necessary to achieve
complete conversion at ambient temperature (Scheme 1).
Thioesters (3, 7, 11) finally were converted to thiols (4, 8, 12) in good yields using
catalytic amount of sodium methoxide in methanol or sodium metal dissolved in
ethylene glycol (Table 2). This method is an analogy of the deacylation process of
sugar acetates which had been elaborated by and named after Zemplén [29] – who
eventually has become the link between the Nobel Laureates Emil Fisher and George
Olah [30].
5

It should be noted, that the deacylation was performed in boiling methanol opposed to
the original Zemplén deacylation condition (in cold solution). This could be interpreted,
that in this case the formed thiol is more acidic than the 1o or 2o hydroxyl groups in the
carbohydrate derivatives (Table 3) and consequently considerable amount of the
catalyst (NaOCH3) is converted to methanol with the simultaneous formation of sodium
thiolate. Thus the amount and concentration of the catalyst decreases and as a
consequence the rate of deacylation also decreases. Since the higher acidity of
RfnCH2SH type thiols, the method of using catalytic amount of sodium methoxide or
alkoxide is not working well. The solvolysis equilibrium can be shifted by continuous
distillation of the thiol from the reaction mixture. (Scheme 2).
Volatile thiols 12a-c were obtained in good yield applying this ‘deprotection with
distillation’ protocol for thioacetates 11a-c. However, the preparation of less volatile
thiols 12d-e was effective by using equivalent amount of NaOCH3 for deprotection of
thioacetates 11d-e.
3. Conclusion
In conclusion, a series of fluorous thiols were synthesized by the nucleophilic
substitution reaction of the appropriate active esters with potassium thioacetate
followed by the base catalyzed alcoholysis of the fluorous thioacetate intermediates
(3a-d, 7, 11a-e). The amount of sodium methoxide and the technique of deprotection
was increased and/or changed to reactive distillation from ethylene glycol,
6

respectively, to enable the easy separation of the most acidic (perfluoroalkyl)methane
thiols (12a-e) as well. All synthesized compounds were fully characterized.
4. Experimental Section
F-Alcohols 1a-d [36], iodides 2a-d [25], tosylate 6 [26b], and triflates 10d-e [37] were
prepared as reported, while F-alcohols 5 and 9a-e were purchased from Fluorochem.
Nonaflates 10a-c were prepared by adaptation of a patented method (Section 4.1;
[27b]). NMR spectra (1H, 19F, 13C) were recorded on a Bruker Avance 250 MHz
instrument at room temperature (295 ± 2 K) in CDCl3. Chemical shifts (δ) are given in
1
ppm units relatively to the internal standards: TMS (δ = 0.00 for H) and CFCl3 (δ =
0.00 for 19F). IR spectra were recorded by a Bruker IFS 28 Fourier transform infrared
(FT-IR) spectrometer with ATR technique. The instrument is equipped with a Globar
source, a KBr beam splitter, and a DTGS detector. At least 32 scans were accumulated
at 4 cm-1 resolution in the 4000-550 cm-1 spectral window. Melting points were
determined on a Boetius micro melting point apparatus and are uncorrected. Purity of
products were determined by GC (Hewlett-Packard 5890 Series II; PONA [crosslinked
methylsilicon gum] 50m×0.2mm× 0.5mm column, H2 carrier gas, FID detection); the
liquid ones with neat injection.
4.1 General procedure for the synthesis of (perfluoroalkyl)methylnonaflates (GP-1)
To the solution of KOH (assay: 85%, 3.92 g, 62 mmol) in water (15 mL) 1H,1H-
perfluoroalkyl alcohol (52 mmol) was added at 0 °C. Then perfluorobutanesulfonyl
fluoride (NfF, 11 mL, 18.72 g, 62 mmol) was added dropwise to the stirred mixture at
5-15 °C. The reaction mixture was stirred for 22h, and the precipitated salts were
7

filtered and washed with water (15 mL.) The two liquid phase filtrate was separated;
the lower phase was washed with water (2 × 10 mL) and dried over Na2SO4 to give
the product.
4.1.1 2,2,2-Trifluoroethyl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate (10a)
According to GP-1 a solution of 9a (3.97 mL, 5.20 g, 52 mmol) in 20 m/m% KOH (20
mL) was reacted with NfF (11.14 mL, 18.72 g, 62 mmol). Yield: 17.88 g (90%),
colorless liquid, bp 140 °C (@ atmospheric pressure). (Lit. [38] bp 60°C/3.75 mmHg).
GC assay: 98.2 %.
1H NMR (250 MHz, CDCl3): δ 4.72 (q, 2H, 3JHF = 7.4 Hz, CF2CH2O).13C NMR (75 MHz,
CDCl3): δ 69.2 (q, 2JCF = 40 Hz, CF3CH2O).19F NMR (235 MHz, CDCl3): δ−126.82 (m,
2F, CF3CF2CF2CF2S); −122.03 (m, 2F, CF3CF2CF2CF2S); −110.72 (t, 2F, 3JFF = 14 Hz,
CF3CF2CF2CH2); −81.77 (tt, 3F, 4JFF = 2.1 Hz, 3JFF = 9.9 Hz, CF3CF2CF2CF2); −75.46
(t, 3F, 3JHF = 7.4 Hz, CF3CH2). IR (neat): ν = 1430, 1177, 1142, 1022, 963, 789 cm-1.
4.1.2 2,2,3,3,3-Pentafluoropropyl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate
(10b)
According to GP-1 a solution of 9b (5.18 mL, 7.80 g, 52 mmol) in 20 m% KOH (20 mL)
was reacted with NfF (11.14 mL, 18.72 g, 62 mmol). Yield: 20.22 g (90 %), colorless
liquid, bp 149 °C (@ atmospheric pressure). GC assay: 98.0%.
1H NMR (250 MHz, CDCl3): δ 4.80 (t, 2H, 3JHF = 11 Hz, CF2CH2O).13C NMR (75 MHz,
CDCl3): δ 68.4 (t, 2JCF = 29 Hz, CF3CH2O).19F NMR (235 MHz, CDCl3): δ−126.51 (m,
2F, CF3CF2CF2CF2S); −124.37 (t, 2F, 3JHF = 11 Hz, CF3CF2CF2CF2S); −121.78 (m, 2F,
3
CF3CF2CF2CF2S); −110.39 (t, 2F, JHF = 14 Hz, CF3CF2CH2); −84.10 (s, 3F,
8

CF3CF2CH2); −81.32 (t, 3F, 3JFF = 9 Hz, CF3CF2CF2). IR (neat): ν = 1430, 1196, 1142,
999, 736 cm-1.
4.1.3 2,2,3,3,4,4,4-Heptafluorobutyl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate
(10c)
According to GP-1 a solution of 9c (5.18 mL, 7.80 g, 52 mmol) in 20 m% KOH (20 mL)
was reacted with NfF (11.14 mL, 18.72 g, 62 mmol). Yield: 21.67 g (86 %), colorless
liquid, bp 152 °C (@ atmospheric pressure). (Lit. [39] 140-150oC). GC assay: 98.3%.
1H NMR (250 MHz, CDCl3): δ 4.84 (t, 2H, 3JHF = 12 Hz, CF2CH2O).13C NMR (75 MHz,
CDCl3): δ 68.5 (t, 2JCF = 28 Hz, CF3CH2O).19F NMR (235 MHz, CDCl3): δ −127.80 (m,
2F, CF3CF2CF2CF2S); −126.49 (m, 2F, CF3CF2CF2CH2);−121.75 (m, 2F,
3
CF3CF2CF2CF2S);−121.31 (m, 2F, CF3CF2CF2CF2S);−110.37 (t, 2F, JHF = 14 Hz,
CF3CF2CF2CH2); −81.30 (m, 6F, CF3CF2CF2CF2, CF3CF2CF2CH2). IR (neat): ν = 1431,
1353, 1199, 1124, 1007, 916, 737 cm-1.
4.2 General Procedure for the Synthesis of 3-(perfluoroalkyl)propylethanethioates
(GP-2)
To the stirred solution or emulsion of 3-(perfluoroalkyl)propyl iodides (2a-d) (15 mmol)
in DMF (25–70 mL) KSAc (2.052 g, 18 mmol) was added at room temperature. The
reaction mixture was stirred several hours at ambient temperature or heated to 80oC
for 0.5-2 h. Then water (75-100 mL) was added and the mixture was extracted with
Et2O (3×15-50 mL). The combined organic phases were washed with water (2×25 mL)
and brine (25 mL) and were dried over Na2SO4. The solvent was evaporated, and the
crude product was purified by short-path distillation.
9

4.2.1 S-(4,4,5,5,6,6,7,7,7-Nonafluoroheptyl) ethanethioate (p. n. c. 3a
)
Iodide 2a (5.82g, 15mmol) was reacted with KSAc (2.05 g, 18 mmol) in DMF (25 mL)
according to GP-2 at 80 °C for 0.5 h and worked up (75 mL H2O & 3 × 30 mL Et2O) to
yield 4.34 g (86%) yellow oil, bp 65-70°C/1 mmHg; GC assay: 98.1%
1H NMR (250 MHz, CDCl3): δ 1.92 (m, 2H, CF2CH2CH2CH2S); 2.14 (m, 2H,
3
CF2CH2CH2CH2S); 2.35 (s, 3H, SC(O)CH3); 2.96 (t, 2H, JHH = 6.9 Hz,
CF2CH2CH2CH2S).13C NMR (62 MHz, CDCl3): δ 20.9 (s, CF2CH2CH2CH2S); 28.2 (s,
CF2CH2CH2CH2S); 29.9 (t, 2JCF = 22 Hz, CF2CH2CH2CH2S); 30.6 (s, SC(O)CH3); 195.2
(s, SC(O)CH3).19F NMR (235 MHz, CDCl3):
δ -126.73 (m, 2F, CF3CF2CF2CF2); -
125.09 (m, 2F, CF3CF2C
F
2CF2); -115.00 (m, 2F, CF3CF2CF2C
F2); -81.79 (tt, 3F,
3JFF = 9.7 Hz, 4JFF = 3.2 Hz, C
F
3CF2CF2CF2). IR (neat): ν = 1698, 1458, 1103, cm-1.
4.2.2 S-(4,4,5,5,6,6,7,7,8,8,9,9,9-Tridecafluorononyl) ethanethioate (n. c. 3b
)
Iodide 2b (20g, 41 mmol) was reacted with KSAc (5.62 g, 49.2 mmol) in DMF (100 mL)
according to GP-2 at 80 °C for 0.5 h and worked up (200 mL H2O & 3×40 mL Et2O) to
yield 16.3 g (91%) yellowish oil, bp 90-100°C/1 mmHg; GC assay: 97.1%
1H NMR (250 MHz, CDCl3): δ 1.91 (m, 2H, CF2CH2CH2CH2S); 2.16 (m, 2H,
3
CF2CH2CH2CH2S); 2.36 (s, 3H, SC(O)CH3); 2.96 (t, 2H, JHH = 7.0 Hz,
CF2CH2CH2CH2S).13C NMR (62 MHz, CDCl3): δ 20.9 (s, CF2CH2CH2CH2S); 28.2 (s,
CF2CH2CH2CH2S); 29.9 (t, 2JCF = 22 Hz, CF2CH2CH2CH2S); 30.7 (s, SC(O)CH3); 195.4
(s, SC(O)CH3).19F NMR (235 MHz, CDCl3):
124.10 (m, 2F, CF3CF2C 2(CF2)3); -123.54 (m, 2F, CF3CF2CF2C
2CF2); -114.77 (m, 2F, CF3(CF2)4C 2); -81.55 (tt, 3F,
3(CF2)5). IR (neat): ν = 1699, 1458, 1073 cm-1
δ
-126.83 (m, 2F, CF3CF2(CF2)4); -
F
F
2CF2CF2); -
122.56 (m, 2F, CF3(CF2)3C
F
F
3JFF = 10.0 Hz, 4JFF = 2.4 Hz, C
F
.
10

4.2.3
S-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl)
ethanethioate (3c)
Iodide 2c (40 g, 68 mmol) was reacted with KSAc (9.34 g, 81.8 mmol) in DMF (250
mL) according to GP-2 at ~20oC for 2 h and worked up (400 mL H2O & 3×200 mL Et2O)
to yield 33.29 g (91%) yellow liquid, bp 120-130°C/1 mmHg; GC assay: 98.9%.
Showed agreeable spectral properties to that reported [8b].
1H NMR (250 MHz, CDCl3): δ 1.91 (m, 2H, CF2CH2CH2CH2S); 2.16 (m, 2H,
3
CF2CH2CH2CH2S); 2.36 (s, 3H, SC(O)CH3); 2.96 (t, 2H, JHH = 7.0 Hz,
CF2CH2CH2CH2S).13C NMR (62 MHz, CDCl3): δ 20.9 (s, CF2CH2CH2CH2S); 28.2 (s,
CF2CH2CH2CH2S); 29.9 (t, 2JCF = 22 Hz, CF2CH2CH2CH2S); 30.7 (s, SC(O)CH3); 195.4
(s, SC(O)CH3).19F NMR (235 MHz, CDCl3):
124.08 (m, 2F, CF3CF2CF2(CF2)5); -123.40 (m, 2F, CF3CF2CF2CF2(CF2)4); -122.57
δ -126.83 (m, 2F, CF3CF2(CF2)6); -
(m, 6F, CF3(CF2)3CF2CF2CF2CF2); -114.78 (m, 2F, CF3(CF2)6CF2); -81.51 (t, 3F,
3JFF = 10.1 Hz, CF3(CF2)7). IR (neat): ν = 1699, 1458, 1066 cm-1
.
4.2.4 S-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,13-Henicosafluorotridecyl)
ethanethioate 3d
(
)
Iodide 2d (10.32 g, 15mmol) was reacted with KSAc (2.05 g, 18 mmol) in DMF (70 mL)
according to GP-2 (80 °C/ 0.5 h) and worked up (100 mL H2O & 3×50 mL Et2O) to yield
6.50 g (68%) white solid, mp 56-67°C; Lit. [8b] mp = 66oC; bp 140-150°C/1mmHg;
GC assay: 98.1%. Showed agreeable spectral properties to that reported [8b].
1H NMR (250 MHz, CDCl3): δ 1.91 (m, 2H, CF2CH2CH2CH2S); 2.16 (m, 2H,
3
CF2CH2CH2CH2S); 2.36 (s, 3H, SC(O)CH3); 2.96 (t, 2H, JHH = 7.0 Hz,
CF2CH2CH2CH2S).13C NMR (62 MHz, CDCl3): δ 20.9 (s, CF2CH2CH2CH2S); 28.2 (s,
CF2CH2CH2CH2S); 29.9 (t, 2JCF = 22 Hz, CF2CH2CH2CH2S); 30.7 (s, SC(O)CH3); 195.4
(s, SC(O)CH3).19F NMR (235 MHz, CDCl3):
δ
-126.57 (m, 2F, CF3C
F
2(CF2)8); -
11

123.90 (m, 2F, CF3CF2C
F
2(CF2)7); -123.15 (m, 2F, CF3CF2CF2C
2C 2C 2C 2CF2); -114.55 (m, 2F, CF3(CF2)8C
3(CF2)7). IR (neat): ν = 1697, 1458, 1078 cm-1
F
2(CF2)6); -122.22
(m, 10F, CF3(CF2)3C
F
2C
F
F
F
F
F
2); -81.21
(t, 3F, 3JFF = 9.9 Hz, C
F
.
4.3 S-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluorooctyl) ethanethioate (7)
A solution of 6 (15.6 g, 30 mmol) or C6F13CH2CH2I (14.2 g, 30 mmol) was reacted with
KSAc (4.00 g, 35 mmol) in DMF (120 mL) according to GP-2 at room temperature for
3 h and worked up (360 mL H2O & 3×200 mL Et2O) to yield 10.8 g (88%) or 9.91 g
(78%) of 7, yellow liquid, bp 55-57°C/3 mmHg; GC assay: 98.1% or 98.4%,
respectively. Products showed agreeable spectral properties to that reported [19a].
1H NMR (250 MHz, CDCl3): δ 2.37 (s, 3H, SC(O)CH3); 2.40 (m, 2H, CF2CH2CH2S);
3.10 (m, 2H, CF2CH2CH2CH2S).13C NMR (62 MHz, CDCl3): δ 20.5 (s, CF2CH2CH2S);
2
32.0 (t, JCF = 22 Hz, CF2CH2CH2S); 30.8 (s, SC(O)CH3); 195.1 (s, SC(O)CH3).19
F
NMR (235 MHz, CDCl3):
δ -126.66 (m, 2F, CF3CF2(CF2)4); -123.98 (m, 2F,
CF3CF2CF2(CF2)3); -123.39 (m, 2F, CF3CF2CF2CF2CF2CF2); -122.41 (m, 2F,
2); -81.33 (tt, 3F, 3JFF = 10.0 Hz,
5JFF = 2.5 Hz, CF3(CF2)5). IR (neat): ν = 1702, 1441, 1073 cm-1
CF3(CF2)3CF2CF2); -115.12 (m, 2F, CF3(CF2)4CF
.
4.4 General procedure for the synthesis of (perfluoroalkyl)methyl ethanethioates (GP-
3)
To the solution of the nonaflate (10a-c) or triflate (10d-e) (15 mmol) in DMF (25 mL)
KSAc (2.052 g, 18 mmol) was added at 10 °C. The reaction mixture was stirred for 1h
then allowed to warm to rt and stirred for additional 1h. Then water (75 mL) was added
and the mixture was extracted with Et2O (3 × 75 mL). The combined organic phases
were washed with water (2 × 50 mL) and brine (50 mL) and were dried over Na2SO4.
12

The solvent was evaporated, and the crude product was purified by short-path
distillation.
4.4.1 S-(2,2,2-Trifluoroethyl) ethanethioate (11a)
The reaction of 10a (5.74g, 15 mmol) with KSAc (2.052 g, 18 mmol) according to GP-
3 afforded 1.71 g (72%) pale yellow liquid, bp 117-120 °C (@ atmospheric pressure).
Lit. bp 115oC [40].
3
1H NMR (250 MHz, CDCl3): δ 3.58 (q, 2H, JHF = 9.9 Hz, CF3CH2S); 2.42 (s, 3H,
2
SC(O)CH3). 13C NMR (75 MHz, CDCl3): δ 29.8 (s, C(O)CH3); 30.6 (q, JCF = 34 Hz,
1
CF3CH2S); 124.7 (q, JCF = 276 Hz, CF3CH2S); 191.6 (s, C(O)CH3). 19F NMR (235
3
MHz, CDCl3): δ −67.05 (t, 3F, JHF = 9.9 Hz, CF3CH2S). IR (neat): ν = 1711, 1309,
1271, 1241, 1121, 1082, 957, 847 cm-1.
4.4.2 S-(2,2,3,3,3-Pentafluoropropyl) ethanethioate(11b)
The reaction of 10b (6.48 g, 15 mmol) with KSAc (2.052 g, 18 mmol) according to GP-
3 afforded 2.10g (67%) pale yellow liquid, bp 45-55 °C/16 mmHg. GC assay: 98.0%.
Showed agreeable spectral properties to that reported [41].
3
1H NMR (250 MHz, CDCl3): δ 2.43 (s, 3H, SC(O)CH3); 3.59 (t, 2H, JHF = 16.8 Hz,
2
CF2CH2S). 13C NMR (75 MHz, CDCl3): δ 29.1 (t, JCF = 24 Hz, CF2CH2S); 30.4 (s,
3
C(O)CH3); 192.1 (s, C(O)CH3). 19F NMR (235 MHz, CDCl3): δ −116.70 (t, 2F, JHF
=
16.8 Hz, CF3CF2CH2); −85.01 (s, 3F, CF3CF2CH2). IR (neat): ν = 1713, 1354, 1189,
1084, 1023, 707 cm-1.
4.4.3 S-(2,2,3,3,4,4,4-Heptafluorobutyl) ethanethioate (n.c. 11c)
13

The reaction of 10c (7.23 g, 15 mmol) with KSAc (2.052 g, 18 mmol) according to GP-
3 afforded 2.91 g (75%) pale yellow liquid, bp 55-62°C/16 mmHg. GC assay: 98.1%.
3
1H NMR (250 MHz, CDCl3): δ 2.43 (s, 3H, SC(O)CH3); 3.63 (t, 2H, JHF = 17.4 Hz,
2
CF2CH2S). 13C NMR (75 MHz, CDCl3): δ 29.4 (t, JCF = 24 Hz, CF2CH2S); 30.5 (s,
C(O)CH3); 192.2 (s, C(O)CH3). 19F NMR (235 MHz, CDCl3): δ −127.55 (m, 2F,
3
CF3CF2CF2CH2); −113.88 (m, 2F, CF3CF2CF2CH2);−81.09 (t, 3F, JFF 9.6 Hz,
CF3CF2CF2CH2). IR (neat): ν = 1715, 1352, 1214, 1113, 1079, 962, 709 cm-1.
4.4.4 S-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl) ethanethioate (n. c.
11d
)
The reaction of 10d (7.99 g, 15 mmol) with KSAc (2.052 g, 18 mmol) according to GP-
3 afforded 6.20 g (90%) pale yellow liquid, bp 85-90°C/1 mmHg. GC assay: 98.0%.
3
1H NMR (250 MHz, CDCl3): δ 2.44 (s, 3H, SC(O)CH3); 3.65 (t, 2H, JHH = 17.4 Hz,
2
CF2CH2S). 13C NMR (62 MHz, CDCl3): δ 29.5 (t, JCF = 24 Hz, CF2CH2S); 30.2 (s,
SC(O)CH3); 191.9 (s, SC(O)CH3).19F NMR (235 MHz, CDCl3): −126.60 (m, 2F,
CF3CF2(CF2)5CH2); −123.10 (m, 4F, CF3CF2CF2
C
F2(CF2)3CH2); −122.51 (m, 2F,
2CF2CH2); −112.84 (m, 2F,
CF3(CF2)3C
CF3(CF2)5C
F
F
2(CF2)2CH2); −122.05 (m, 2F, CF3(CF2)4C
2CH2); −81.22 (t, 3F, 3JFF 9.8 Hz, C
F
F
3(CF2)6CH2). IR (neat): ν = 1720,
1408, 1089 cm-1
.
4.4.5 S-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-Hexadecafluorononyl) ethanethioate (n. c.
11e
)
The reaction of 10e (8.46 g, 15 mmol) with KSAc (2.052 g, 18 mmol) according to GP-
3 afforded 6.49g (88%) pale yellow liquid, bp 100-110°C/1 mmHg. GC assay: 99.0%.
14

3
1H NMR (250 MHz, CDCl3): δ 2.43 (s, 3H, SC(O)CH3); 3.65 (t, 2H, JHH = 17.4 Hz,
2
CF2CH2S); 6.05 (tt, 1H, JHF = 17.4 Hz, 3JHF = 17.4 Hz, H(CF2)8). 13C NMR (62 MHz,
CDCl3): δ 29.5 (t, 2JCF = 24 Hz, CF2CH2S); 30.1 (s, SC(O)CH3); 192. (s, SC(O)CH3).19
F
NMR (235 MHz, CDCl3):
δ
−137.48 (d, 2F, 3JFH 51.9 Hz, HCF2(CF2)7CH2); −129.84
(m, 2F, CF2(CF2)6CH2); −123.81 (m, 2F, CF2(CF2)5CH2); −123.08 (m, 2F,
C
F2(CF2)4CH2); −122.39 (m, 4F, CF2CF2(CF2)2CH2); −122.03 (m, 2F, CF2CF2CH2);
−112.85 (m, 2F, (CF2)7CF2CH2). IR (neat): ν = 1719, 1407, 1088 cm-1
.
4.5 General procedure for the synthesis of 3-(perfluoroalkyl)propane-1-thiols (GP-4)
The solution of 3a-d (15mmol) in methanol (45-75 mL) was deoxygenated by N2
or Ar gas then NaOCH3 (0.75mmol) was added. The reaction mixture was refluxed
for 1.5h under N2 or Ar atmosphere then the product isolated by fractional
distillation.
4.5.1 4,4,5,5,6,6,7,7,7-Nonafluoroheptane-1-thiol (4a
)
The deprotection of 3a (5.04 g, 15 mmol) in 45 mL methanol according to GP-4
afforded 3.05 g (69 %), pale yellow liquid, bp 50-60°C/1 mmHg. GC assay: 98.8%.
Cf. [42].
1H NMR (250 MHz, CDCl3): δ 1.38 (t, 1H, 3JHH = 8.2 Hz, CF2CH2CH2CH2SH); 1.94 (m,
2H, CF2CH2CH2CH2SH); 2.22 (m, 2H, CF2CH2CH2CH2SH); 2.63 (dt, 2H, 3JHH = 8.2 Hz,
3JHH = 6.9 Hz, CF2CH2CH2CH2SH). 13C NMR (62 MHz, CDCl3): δ 24.0 (s,
2
CF2CH2CH2CH2S); 24.8 (s, CF2CH2CH2CH2S); 29.5 (t, JCF
=
22 Hz,
CF2CH2CH2CH2S).19F NMR (235 MHz, CDCl3):
δ
-126.59 (m, 2F, CF3C
F
2CF2CF2);
-124.96 (m, 2F, CF3CF2C
F2CF2); -114.80 (m, 2F, CF3CF2CF2CF2); -81.61 (t, 3F,
3JFF = 9.7 Hz, C 3CF2CF2CF2). IR (neat): ν = 2567, 1457, 1134 cm-1
F
.
15

4.5.2 4,4,5,5,6,6,7,7,8,8,9,9,9-Tridecafluorononane-1-thiol (4b
)
The deprotection of 3b (6.54 g, 15 mmol) in 60 mL methanol according to GP-4
afforded 4.56 g (77%), pale yellow liquid, bp 80-90°C/1 mmHg. GC assay: 95.7%.
Showed agreable spectral properties to that reported [12].
1H NMR (250 MHz, CDCl3): δ 1.39 (t, 1H, 3JHH = 8.2 Hz, CF2CH2CH2CH2SH); 1.94 (m,
2H, CF2CH2CH2CH2SH); 2.24 (m, 2H, CF2CH2CH2CH2SH); 2.63 (dt, 2H, 3JHH = 8.2 Hz,
3JHH = 6.9 Hz, CF2CH2CH2CH2SH). 13C NMR (62 MHz, CDCl3): δ 24.0 (s,
2
CF2CH2CH2CH2S); 24.8 (s, CF2CH2CH2CH2S); 29.6 (t, JCF
=
22 Hz,
CF2CH2CH2CH2S).19F NMR (235 MHz, CDCl3):
δ
-126.76 (m, 2F, CF3C
F
2(CF2)4); -
124.05 (m, 2F, CF3CF2C
F
2(CF2)3); -123.46 (m, 2F, CF3(CF2)2CF2(CF2)2); -122.49
(m, 2F, CF3(CF2)3C
Hz, CF3(CF2)5). IR (neat): ν = 2566, 1457, 1075 cm-1
F2CF2); -114.63 (m, 2F, CF3(CF2)4CF
2); -81.42 (t, 3F, 3JFF = 9.9
.
4.5.3
4c
4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecane-1-thiol
(
)
The deprotection of 3c (8.04 g, 15 mmol) in 75 mL methanol according to GP-4
afforded 5.93g (80%), pale yellow liquid, bp 90-100°C/5 mmHg. Lit. [10] bp 60-
66°C/0.75mmHg. GC assay: 98.0%.
1H NMR (250 MHz, CDCl3): δ 1.38 (t, 1H, 3JHH = 8.2 Hz, CF2CH2CH2CH2SH); 1.94 (m,
2H, CF2CH2CH2CH2SH); 2.24 (m, 2H, CF2CH2CH2CH2SH); 2.63 (dt, 2H, 3JHH = 8.2 Hz,
3JHH = 7.0 Hz, CF2CH2CH2CH2SH). 13C NMR (62 MHz, CDCl3): δ 24.1 (s,
2
CF2CH2CH2CH2S); 24.9 (s, CF2CH2CH2CH2S); 29.7 (t, JCF
=
22 Hz,
CF2CH2CH2CH2S).19F NMR (235 MHz, CDCl3):
δ
-126.91 (m, 2F, CF3C
F
2(CF2)6); -
124.16 (m, 2F, CF3CF2C 2(CF2)5); -123.46 (m, 2F, CF3(CF2)2CF2(CF2)4); -122.63
F
(m, 6F, CF3(CF2)3(C
F
2)3CF2); -114.76 (m, 2F, CF3(CF2)6C
F
2); -81.63 (t, 3F, 3JFF =
9.5 Hz, C
F
3(CF2)7).IR (neat): ν = 2566(w), 1457, 1115 cm-1
.
16

4.5.4
4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,13-
Henicosafluorotridecane-1-thiol (4d
)
The deprotection of 3d (9.54 g, 15 mmol) in 75 mL methanol according to GP-4
afforded 7.22 g (81 %), pale yellow waxy solid, mp 61-62°C, bp 120-130°C/1
mmHg. GC assay: 98.1%. Showed agreeable spectral properties to that reported [8b].
1H NMR (250 MHz, CDCl3): δ 1.38 (t, 1H, 3JHH = 8.2 Hz, CF2CH2CH2CH2SH); 1.94 (m,
2H, CF2CH2CH2CH2SH); 2.24 (m, 2H, CF2CH2CH2CH2SH); 2.63 (dt, 2H, 3JHH = 8.2 Hz,
3JHH = 7.0 Hz, CF2CH2CH2CH2SH).13C NMR (62 MHz, CDCl3): δ 24.2 (s,
2
CF2CH2CH2CH2S); 25.0 (s, CF2CH2CH2CH2S); 29.8 (t, JCF
=
22 Hz,
CF2CH2CH2CH2S).19F NMR (235 MHz, CDCl3):
δ
-126.56 (m, 2F, CF3C
F
2(CF2)8); -
123.90 (m, 2F, CF3CF2CF2(CF2)7); -123.16 (m, 2F, CF3(CF2)2CF2(CF2)6); -122.22
3
(m, 10F, CF3(CF2)3(CF2)5CF2); -114.46 (m, 2F, CF3(CF2)8CF2); -81.20 (t, 3F, JFF
= 10.0 Hz, CF3(CF2)9). IR (neat): ν = 2566 (w), 1456, 1110 cm-1
.
4.6 3,3,4,4,5,5,6,6,7,7,8,8,8-Tridecafluorooctane-1-thiol (
8)
The solution of (9.00 g, 21 mmol) in methanol (50 mL) was deoxygenated by Ar
7
for 5 min then NaOCH3 (0.35 g, 6.5mmol) was added. The mixture was refluxed for
3 h under an Ar atmosphere and then the product was isolated by fractional
distillation. Yield: 7.12 g (88 %), pale yellow liquid, bp 60-65°C/16 mmHg.GC assay:
98.2%. Lit. bp 61oC/10 mmHg [19a] and bp 120oC/760 mmHg [43]. Showed agreeable
spectral properties to that reported [19a].
3
1H NMR (250 MHz, CDCl3): δ 1.60 (t, 1H, JHH = 8.4 Hz, CF2CH2SH); 2.42 (m, 2H,
CF2CH2CH2SH); 2.78 (dt, 2H, 3JHH = 8.4 Hz, 3JHH = 8.0 Hz, CF2CH2CH2SH). 13C NMR
2
(62 MHz, CDCl3): δ 15.7 (s, CF2CH2CH2S); 36.2 (t, JCF = 22 Hz, CF2CH2CH2S). 19F
NMR (235 MHz, CDCl3):
δ
-126.62 (m, 2F, CF3CF2(CF2)4); -123.83 (m, 2F,
17

CF3CF2C
F
2(CF2)3); -123.36 (m, 2F, CF3CF2CF2C
F
2CF2CF2); -122.40 (m, 2F,
3
CF3(CF2)3C
F
2CF2); -114.20 (m, 2F, CF3(CF2)4C
F
2); -81.28 (t, 3F, JFF = 9.9 Hz,
C
F
3(CF2)5). IR (neat): ν = 2566(w), 1447, 1074 cm-1
.
4.7 General procedure for the synthesis of 1H,1H-perfluoroalkane-1-thiols
Method A (GP-5A).
In a 10 mL volume flask under an N2 atmosphere sodium metal (11.5 mg,
0.5 mmol) was dissolved in ethyleneglycol (5.0 mL) with stirring, then after
addition of thioacetate 11a-c (10 mmol) it was refluxed for 2h then the
volatile products were isolated by short-path atmospheric distillation.
Method B (GP-5B).
Under an N2 atmosphere to the stirred solution of thioacetate 11d-e (15 mmol) in
methanol (60 mL) NaOCH3 (15 mmol) was added and the mixture was refluxed for
5 h. The solvent was removed by distillation and the residue was treated with water
(30 mL) and acidified with 6M HCl (5.0 mL), then extracted with ether (3×15 mL).
The combined extracts were dried (Na2SO4), and the product was isolated by
distillation.
4.7.1 2,2,2-Trifluoroethanethiol (12a)
The deprotection of 11a (1.58 g, 10mmol) according to GP-5A afforded 0.84 g (72 %),
colorless liquid, bp 35-40 °C (@ atmospheric pressure). Lit. bp 36.5oC, [18b]; 35-
36oC [44]. GC assay: 98.2%.
3
1H NMR (250 MHz, CDCl3): δ 1.74 (t, 3JHH = 9.0 Hz, 1H, SH); 3.01 (q, 2H, JHF = 9.4
Hz, CF3CH2S).13C NMR (75 MHz, CDCl3): δ 27.7 (t, 2JCF = 35 Hz, CF3CH2S);125.5 (t,
18

1JCF = 274 Hz, CF3CH2S). 19F NMR (235 MHz, CDCl3): δ −69.69 (t, 3F, 3JHF = 9.4 Hz,
CF2CH2S). IR (neat): ν = 2928, 2362 (w), 1716, 1407, 1125, 1072 cm-1
.
4.7.2 2,2,3,3,3-Pentafluoropropane-1-thiol (12b)
The deprotection of 11b (2.08 g, 10 mmol) according to GP-5A afforded 1.24 g (75
%), colorless liquid, bp 45-55 °C (@ atmospheric pressure). Lit. bp 45-47 oC [18b].
GC assay: 98.1%.
1H NMR (250 MHz, CDCl3): δ1.75 (t, 3JHH = 9.1 Hz, 1H, SH); 3.09 (dt, 2H, 3JHH = 9.1
Hz, 3JHF = 16.5 Hz, CF3CF2CH2S). 13C NMR (75 MHz, CDCl3): δ 25.6 (t, 2JCF = 25 Hz,
CF3CF2CH2S). 19F NMR (235 MHz, CDCl3): δ −84.74 (s, 3F, CF3CF2CH2); −119.47 (t,
2F, 3JHF = 16.2 Hz, CF3CF2CH2). IR (neat): ν = 2584 (w), 1716, 1187, 1104, 1021 cm-
1.
4.7.3 2,2,3,3,4,4,4-Heptafluorobutane-1-thiol (12c)
The deprotection of 11c (2.58 g, 10 mmol) according to GP-5A afforded 1.71 g (79
%), colorless liquid, bp 70-75 °C (@ atmospheric pressure). Lit. bp 75-76oC [18b].
GC assay: 98.0%.
3
3
4
1H NMR (250 MHz, CDCl3): δ 3.13 (tdt, 2H, JHF = 16.7 Hz, JHH = 9.1 Hz, JHF = 1.3
Hz, CF2CF2CH2S); 1.74 (t, 3JHF = 9.1 Hz, 1H, SH). 13C NMR (75 MHz, CDCl3): δ 25.7
2
(t, JCF = 25 Hz, CF3CF2CF2CH2S). 19F NMR (235 MHz, CDCl3): δ −127.58 (m, 2F,
3
CF3CF2CF2CH2); −116.67 (m, 2F, CF3CF2CF2CH2); −81.20 (t, 3F, JFF 9.6 Hz,
CF3CF2CF2CH2). IR (neat): ν = 2584 (w), 1717, 1352, 1214, 1112, 961 cm-1
.
4.7.4 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-Pentadecafluorooctane-1-thiol (p.n.c. 12d
)
19

The deprotection of 11d (6.87 g, 15 mmol) according to GP-5B afforded 4.70g (75 %),
pale yellow liquid, bp 65-70 °C/16 mmHg. GC assay: 98.1%.
1H NMR (250 MHz, CDCl3): δ 1.75 (t, 1H, 3JHH = 8.1 Hz, CF2CH2SH); 3.14 (td, 2H, 3JHF
= 16.7 Hz, 3JHH = 8.1 Hz, CF2CH2SH). 13C NMR (62 MHz, CDCl3): δ 25.8 (t, 2JCF = 26
Hz, CF2CH2S).19F NMR (235 MHz, CDCl3):
δ -126.63 (m, 2F, CF3CF2(CF2)5); -
123.17 (m, 4F, CF3CF2(CF2)2(CF2)3); -122.52 (m, 2F, CF3(CF2)3CF2(CF2)2); -
122.04 (m, 2F, CF3(CF2)4CF2CF2); -113.60 (m, 2F, CF3(CF2)5CF2); -81.20 (t, 3F,
3JFF = 9.8 Hz, C 3(CF2)6). IR (neat): ν = 2582, 1422, 1104 cm-1
F .
4.7.5 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-Hexadecafluorononane-1-thiol (n.c. 12e
)
The deprotection of 11e (7.53 g, 15 mmol) according to GP-5B afforded 4.72 g (70
%), pale yellow liquid, bp 90-100 °C/16 mmHg. GC assay: 97.9%.
1H NMR (250 MHz, CDCl3): δ 1.74 (t, 1H, 3JHH = 9.0 Hz, CF2CH2SH); 3.14 (td, 2H, 3JHH
3
2
3
= 16.6 Hz, JHF = 9.1 Hz, CF2CH2SH); 6.04 (tt, 1H, JHF = 51.9 Hz, JHF = 5.1 Hz,
2
H(CF2)8CH2SH). 13C NMR (62 MHz, CDCl3): δ 25.8 (t, JCF = 26 Hz, CF2CH2S). 19F
NMR (235 MHz, CDCl3):
δ
-137.57 (d, 2F, 3JFH = 51.9 Hz, HC
2(CF2)5); -123.21 (m, 2F,
F2(CF2)7); -129.91 (m,
2F, HCF2C 2(CF2)6); -123.88 (m, 2F, H(CF2)2C
F
F
H(CF2)3C
F
F
2(CF2)4); -122.50 (m, 4F, H(CF2)4C
F2CF2(CF2)2); -122.16 (m, 2F,
H(CF2)6C
2CF2); -115.79 (m, 2F, H(CF2)7C
F
2). IR (neat): ν = 2582, 1421, 1106 cm-
1
.
Acknowledgement
This work was financed by the National Research, Development and Innovation Office
(NKFIH) as part of the M.ERA-NET transnational COR_ID program (NN 117633).
20

References
[1) I. T. Horváth, J. Rábai, Facile catalyst separation without water: Fluorous biphase
hydroformylation
of
olefins,
Science
266
(1994)
72-75.
DOI:
10.1126/science.266.5182.72 (b) I. T. Horváth, J. Rábai, (to Exxon USA) Fluorous
Multiphase Catalyst or Reagent Systems for Environmentally Friendly Oxidation or
Hydroformylation or Extraction Processes.. Eur. Pat. Appl. (1995), 11 pp. EP 633062
A1
19950111;
(c) Fluorous Chemistry, Volume Editor: Istvan T. Horvath, Vol. 308, 2012; in: Topics in
Current Chemistry, Springer-Verlag Berlin Heidelberg 2012.
[2] J. H. Simons, The Seven Ages of Fluorine Chemistry, J. Fluorine Chem. 32 (1986)
7-24. https://doi.org/10.1016/S0022-1139(00)80503-5.
[3] C.-P. Zhang, Z. Xi, K. M. Mueller, B. J. Holliday, H. S. Bazzi, J. A. Gladysz,;1; Phase
and redox shifted four iron/four sulfur clusters: fluorous analogs of metalloenzyme
cofactors. Dalton Trans. 44 (2015) 19615–19624. DOI: 10.1039/C5DT01959A
[4] (a) Y. Jing, X. Huang Fluorous thiols in oligosaccharide synthesis, Tetrahedron
Lett. 45 (2004) 4615–4618. https://doi.org/10.1016/j.tetlet.2004.04.116;
[5] C. Hiu-Tung Chen, W. Zhang, 2004. 1H,1H,2H,2H-Perfluorodecanethiol. e-EROS.
DOI: 10.1002/047084289X.rn00425
[6] (a) J. Tüxen, S. Eibenberger, S. Gerlich, M. Arndt, M. Mayor, Highly Fluorous
Porphyrins as Model Compounds for Molecule Interferometry, Eur. J. Org. Chem.
(2011) 4823–4833. DOI: 10.1002/ejoc.201100638;
[7] P. Polavarapu, M. P. Krafft, Perfluoroalkylated poly(oxyethylene) thiols: Synthesis,
adsorption dynamics and surface activity at the air/water interface, and bubble
stabilization
behaviour,
J.
Fluorine
Chem.
171
(2015)
12-17.
http://dx.doi.org/10.1016/j.jfluchem.2014.10.020
[8] a) O. Zenasni, A.C. Jamison, T. R. Lee, The impact of fluorination on the structure
and properties of self-assembled monolayer films (Review), Soft Matter, 9 (2013)
6356-6370.
DOI: 10.1039/c3sm00054k;
[9] Y. Yuan, Chi Ming Yam, O. E. Shmakova, R. Colorado, Jr., M. Graupe, H.
Fukushima, H. J. Moore, T. R. Lee, Solution-Phase Desorption of Self-Assembled
Monolayers on Gold Derived From Terminally Perfluorinated Alkanethiols, J. Phys.
Chem. C 115 (2011) 19749–19760. dx.doi.org/10.1021/jp204970b
[10] W. M. Friedlander, W. M.; Fluorocarbon-substituted mercaptans; US Patent
3,088,849 (to Minnesota Mining and Manufacturing Company), May 7, 1963
(application: December 11, 1961).
21

[11] E. Celia, T. Darmanin, E. T. de Givenchy, S. Amigoni, F. Guittard; Recent
advances in designing superhydrophobic surfaces; J. Colloid Interface Sci. 402 (2013)
1-18. DOI: 10.1016/j.jcis.2013.03.041
[12] (a) S. Peroche, G. Degobert, J.-L. Putaux, M.-G. Blanchin, H. Fessi, H. Parrot-
Lopez, Synthesis and characterisation of novel nanospheres made from amphiphilic
perfluoroalkylthio-β-cyclodextrins, Eur. J. Pharm. Biopharm. 60 (2005) 123–131.
doi:10.1016/j.ejpb.2005.01.005
[13] (a) J. Rábai, Fun and Games with Fluorous Chemistry, in Handbook of Fluorous
Chemistry (eds John. A. Gladysz, D. P. Curran and I. T. Horváth), (2004) Wiley-VCH
Verlag GmbH & Co. KGaA, Weinheim, FRG. doi: 10.1002/3527603905.ch14;
[14] K. Ford, B. J. Battersby, B. J. Wood, I. R. Gentle, The production and verification
of pristine semi-fluorinated thiol monolayers on gold, J. Colloid Interface Sci. 370
(2012)
162-169.
doi: 10.1016/j.jcis.2011.10.081
[15] (a) M. Abla, G. Durand, B. Pucci, Glucose-Based Surfactants with Hydrogenated,
Fluorinated, or Hemifluorinated Tails: Synthesis and Comparative Physical-Chemical
Characterization, J. Org. Chem. 2008, 73, 8142–8153; doi: 10.1021/jo801379e
[16] J. L. Wardell, The preparation of thiols, Chapter 4. In: The Chemistry of the Thiol
Group (Ed. S. Patai), John Wiley & Sons Ltd. © 1974; pp. 163-269.
[17] M. Graupe, T. Koini, V. Y. Wang, G. M. Nassif, R. Colorado, Jr., R. J. Villazana,
H. Dong, Y. F. Miura, O. E. Shmakova, T. R. Lee,;1; Terminally perfluorinated long-
chain
alkanethiols,
J.
Fluorine
Chem.
93
(1999)
107-115.
https://doi.org/10.1016/S0022-1139(98)00284-X
[18] (a) Hayashi, T.; Matsuo, H. (to Asahi Glass Co., Ltd., Japan)
Polyfluoroalkanethiols; JP 52118409, A Oct 04, 1977, (Application: Mar 31, 1976).
[19] (a) C. Naud, P. Calas, H. Blancou, A. Commeyras, Synthesis of terminally
perfluorinated long-chain alkanethiols, sulfides and disulfides from the corresponding
halides, J. Fluorine Chem. 104 (2000) 173-183. https://doi.org/10.1016/S0022-
1139(00)00215-3;
[20] (a) S. A. Siry, V. M. Ogurok, Y. G. Shermolovich, Reaction of (2,2,3,3-
tetrafluoropropyl)sulfenyl chloride with ethyl acrylate as a route to functionalized
enamines and ring substituted 3,4-dihydro-2H-thiazine-1,1-dioxides, J. Fluorine Chem.
168 (2014) 137–143. https://doi.org/10.1016/j.jfluchem.2014.09.022
[21] (a) N. Mureau, F. Guittard, S. Géribald, Convenient synthesis of thiols and
disulfides in the polyfluorinated series incorporating a butylic spacer, Tetrahedron Lett.
41 (2000) 2885–2889.
[22] (a) T. Bříza, V. Král, P. Martásek, R. Kaplánek, Electrophilic polyfluoroalkylating
agents based on sulfonate esters, J. Fluorine Chem. 129 (2008) 235–247.
https://doi.org/10.1016/j.jfluchem.2007.11.009.
[23] (a) C. Decroos, C. M. Bowman, D. W. Christianson, Synthesis and evaluation of
N8-acetyl spermidine analogues as inhibitors of bacterial acetylpolyamine
amidohydrolase,
Bioorg.
Med.
Chem.
21
(2013)
4530-4540.
DOI:10.1016/j.bmc.2013.05.045
22

[24] (a) R. L. Hansen, Perfluoroalkanesulfonate Esters as Alkylating Agents, J. Org.
Chem. 30 (1965) 4322-4324. DOI: 10.1021/jo01023a511.
[25] B. Menczinger, G. Jakab, D. Szabó, J. Rábai, Synthesis of 1-iodo-3-
perfluoroalkylpropanes and 1-iodo-4-perfluoroalkylbutanes, Fluorine Notes 94 (2014)
3. http://notes.fluorine1.ru/public/2014/3_2014/letters/letter3.html
[26] (a) J. Rábai, D. Szabó, E. K. Borbás, I. Kövesi, I. Kövesdi, A. Csámpai, Á. Gömöry,
V. E. Pashinnik, Y. G. Shermolovich, Practice of fluorous biphase chemistry:
convenient synthesis of novel fluorophilic ethers via a Mitsunobu reaction, J. Fluorine
Chem. 114 (2002) 199-207. DOI: 10.1016/S0022-1139(02)00027-1
[27] (a) R. L. Hansen, Fluoroalkylperfluoroalkanesulfonates, Fr. (1967), FR 1470669
19670224.(b) M. J. Bulinski, W. M. Lamanna (to 3M Innovative Properties Company);
Aqueous Methods for Making Fluorinated Sulfonate Esters, US Patent Application
Publication, Pub. No.: US 2010/0016624 A1; Pub. Date: Jan. 21, 2010
[28] I. G. Zenkevich, Estimation of Properties of Organic Perfluoroalkyl Derivatives
Using Recurrent Equations, Russian J.Gen. Chem. 85 (2015) 533–544. [Original
Russian Text © I. G. Zenkevich, Zh. Obshchei Khim. 85 (2015) 365–377.] DOI:
10.1134/S1070363215030032
[29] (a) Zemplén Deacetylation. Comprehensive Organic Name Reactions and
Reagents. 691 (2010) 3123–3128. © 1999-2014 by John Wiley and Sons, Inc. DOI:
10.1002/9780470638859
(b) B. Ren, M. Wang, J. Liu, J. Ge, X. Zhang, H. Dong; Zemplén transesterification: a
name reaction that has misled us for 90 years, Green Chem; 17 (2015) 1390-1394;
DOI: 10.1039/C4GC02006E
[30] (a) M. Simonyi, The Legacy of George Olah, Period. Polytech. Chem. Eng. 61
(2017) 301-307. https://doi.org/10.3311/PPch.11352 (accessed: 14.12.2017)
(b) G. K. Surya Prakash, George A. Olah (1927–2017): Master of Carbocations and
Advocate for a Methanol Economy, Angew. Chem. Int. Ed. 56 (2017) 5660 – 5661.
DOI: 10.1002/anie.201703322
[31] T. V. DeCollo, W. J. Lees, Effects of Aromatic Thiols on Thiol-Disulfide
Interchange, Reactions That Occur during Protein Folding, J. Org. Chem. 66 (2001)
4244-4249. pubs.acs.org/doi/abs/10.1021/jo015600a
[32] B. Thapa, H. B. Schlegel, Density Functional Theory Calculation of pKa’s of Thiols
in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum
Model, J. Phys. Chem. A 120 (2016) 5726−5735. DOI: 10.1021/acs.jpca.6b05040
[33] (a) M. H. Abraham, P. L. Grellier, D. V. Prior, P. P. Duce, J. J. Morris, P. J. Taylor,
Hydrogen bonding. Part 7. A scale of solute hydrogen-bond acidity based on logK
values for complexation in tetrachloromethane, J. Chem. Soc., Perkin 2 (1989) 699-
711.
DOI:
10.1039/P29890000699
(b) B.E. Smart, Fluorine substituent effects (on bioactivity), J. Fluorine Chem. 109
(2001) 3-11.
[34] I. Ugur, A. Marion, S. Parant, J. H. Jensen, G. Monard, Rationalization of the pKa
Values of Alcohols and Thiols Using Atomic Charge Descriptors and Its Application to
the Prediction of Amino Acid pKa’s; J. Chem. Inf. Model. 54 (2014) 2200-2213.
dx.doi.org/10.1021/ci500079w |
23

[35] John A. Dean, Lange’s Handbook of Chemistry, 15th edition, McGraw-Hill, New
York, 1999. (Table 8.24, 8-47)
[36] J. Rábai, C. Szíjjártó, P. Ivanko, D. Szabó, 3-(Perfluoroalkyl)propanols: Valuable
Building Blocks for Fluorous Chemistry, Synthesis (2007) 2581-2584; DOI: 10.1055/s-
2007-983779
[37] M. Berta, A. Dancsó, A. Nemes, Z. Pathó, D. Szabó, J. Rábai, Convenient
synthesis of pure fluorous alkylazides at multigram scale, J. Fluorine Chem. 196 (2017)
57-62. https://doi.org/10.1016/j.jfluchem.2016.08.005
[38] F. G. Tournilhac, L. Bosio, J. Simon, L. M. Blinov, S. V. Yablonsky, Synthesis of
polyphilic compounds: Evidence for ferroelectricity in a non-chiral mesophase, Liquid
Crystals, 14 (1993) 405-414. DOI: 10.1080/02678299308027655.
[39] R. M. Flynn, M. J. Bulinski, M. G. Costello (to 3M Innovative Properties Company)
Methods of Making Fluorinated Ethers, Fluorinated Ethers, and Uses Thereof; US
Patent 7,988,877 B2 (Aug. 2, 2011)
[40] M. J. Gregory, T. C. Bruice, Nucleophilic Displacement Reactions at the Thiol
Ester Bond. V. Reactions of 2,2,2-Trifluoroethyl Thiolacetate, J. Am. Chem. Soc. 89
(1967) 2121-2127. DOI:10.1021/ja00985a024.
[41] R. Freter, E. R. Pohl, J. M. Wilson, D. J. Hupe, Role of the central thiol in
determining rates of thethiol-disulfide interchange reaction, J. Org. Chem. 44 (1979)
1771-1774. DOI: 10.1021/jo01325a005
[42] J. Delhalle, Z. Mekhalif, F. Laffineur, S. Noel, N. Lecaude, L. Tristani, D.
Alamarguy, S. Geribaldi, F. Guittard, L. Tortech, Two-layer fluoroalkane-perfluoro
polyether lubricant coatings for lubrication of electric contacts in automobiles and other
vehicles, Fr. Demande (2003), FR 2839316 A1 20031107
[43] S. Y.Dieng, B. Bertaïna, A. Cambon,Synthese et application de nouveaux sulfures
a
chaine
perfluoree,
J.
Fluorine
Chem.,
28
(1985)
341-355.
https://doi.org/10.1016/S0022-1139(00)80545-X
[44] A. Yu. Sizov, A. N. Kovregin, R. N. Serdyuk, M. V. Vorob´ev, V. A. Porosyatnikov,
Synthesis and reactivity of fluorine-containing thiols and thioacyl halides, Russian
Chem. Bull., Int. Ed. 55 (2006) 1200-1208. (In Russian: Izvestiya Akademii Nauk.
Seriya
Khimicheskaya,
No.
7,
pp.
1156—1163,
July,
2006.)
link.springer.com/article/10.1007/s11172-006-0399-4 -Figure Caption
24

Scheme 1. Syntheses of thioacetates and thiols from fluorous alcohols.
25

Scheme 2. Catalytic deprotection with continuous product removal.
26

Table 1. Boiling points of fluorous triflate and nonaflate pairs.
TRIFLATES
B.P.
NONAFLATES
B.P. [°C]
RfnCH2OSO2CF3
CF3CH2- [24a]
[°C/mmHg]
89-91/740
102-105/740
118-120/730
RfnCH2OSO2C4F9
CF3CH2- (10a) (p. n. c.)
CF3CF2CH2- (10b) (p. n. c.)
CF3CF2CF2CH2- (10c) (p. n. c.)
140
149
152
CF3CF2CH2- [24a]
CF3CF2CF2CH2- [24a]
a p. n. c. = prepared or purchased, but not fully characterized
27

Table 2. Selected physical properties and yields of fluorous products (3, 4, 7, 8, 11,
12).
Producta
MW
Boiling Point [oC/mmHg] Yield [%]b
(Lit. value)
Procedure
[g/mol]
3a Rf4-CH2CH2CH2-SAc (p. n. 336.22
65-70/1
86
GP-2
c.)
3b Rf6-CH2CH2CH2-SAc (n. c.) 436.23
90-100/1
91
91
GP-2
GP-2
3c Rf8-CH2CH2CH2-SAc (p. n. 536.25
120-130/1
c.)
3d Rf10-CH2CH2CH2-SAc [8b]
636.26
140-150/1
50-60/1
68
69
GP-2
GP-4
4a Rf4-CH2CH2CH2-SH (p. n. 294.18
c.)
4b Rf6-CH2CH2CH2-SH (n. c.) 394.20
80-90/1
77
80
81
88
53
72
67
75
90
88
72
75
GP-4
GP-4
GP-4
GP-2
GP-4
GP-3
GP-3
GP-3
GP-3
GP-3
GP-5A
GP-5A
4c Rf8-CH2CH2CH2-SH
4d Rf10-CH2CH2CH2-SH
7 Rf6-CH2CH2-SAc (p. n. c.)
8 Rf6-CH2CH2-SH
494.21
594.23
422.21
380.17
158.14
208.16
258.16
458.19
490.20
116.11
166.11
90-100/5 (60-65/0.75 [10])
120-130/1(mp 66 [8b])
55-57/3
60-65/16 (61°C/10 [19a])
117-120 (108–110 [20b])
45-55/16
11a Rf1-CH2-SAc
11b Rf2-CH2-SAc (p. n. c.)
11c Rf3-CH2-SAc (n. c.)
11d Rf7-CH2-SAc (n. c.)
11e H(CF2)8-CH2-SAc (n. c.)
12a Rf1-CH2-SH
55-62/16
85-90/1
100-110/1
35-40 (36.5 [18b])
45-55 (45-47 [18b])
12b Rf2-CH2-SH
28

12c Rf3-CH2-SH
216.12
416.15
448.17
70-75 (75-76 [18b])
65-70/16
79
70
70
GP-5A
GP-5B
GP-5B
12d Rf7-CH2-SH (p.n.c.)
12e H(CF2)8-CH2-SH (n.c.)
90-100/16
a
n. c. = new compound; p.n.c. = prepared or purchased, but not fully characterized.
b The distilled products are of high purity (GC assay: ≥ 98%, cf.: Experimental Section).
Table 3. pKa values of selected thiols and alcohols
Entry
pKa
Lit.
CF3CH2SH
CH3CH2SH
CF3CH2OH
CH3CH2OH
CH3OH
7.30
[31]
[32]
[33]
[33]
[34]
[35]
10.61
12.39
15.93
15.20
14.22
HOCH2CH2OH
29