Synthesis of functionalized long-chain thiols and thiophenols for the formation of self-assembled monolayers on gold

Article abstract of DOI:10.1055/s-1999-3498

The terminally 2-thienyl- and phenyl-substituted eicosane derivatives 4 and 5 were prepared by reacting 1-[(20-bromoeicosyl)oxy]-4-methoxybenzene (3) with 2-lithiothiophene and lithium diphenylcuprate, respectively. Reaction of 4 and 5 with BBr₃ leads to the corresponding bromides 6, 7 which afforded the aryl-substituted eicosanethiols 8 and 9 by nucleophilic substitution with thiourea. 4-Eicosylthiophenol (13) was prepared from eicosylbenzene (11) by chlorosulfonation and subsequent reduction of the sulfonyl chloride. Synthesis of the thiol 22 with phenylenedioxy groups incorporated in the alkyl chain involves formation of 19 from allyloxy(bromobutoxy)benzene (18) and (4-(2-thienyl)butoxy)phenol (17). Hydroboration of 19 yields the corresponding alcohol 20, which under Mitsunobu conditions and subsequent reduction with LiAlH₄ can be transformed to 22.

Full text of DOI:10.1055/s-1999-3498

PAPER
953
Synthesis of Functionalized Long-Chain Thiols and Thiophenols for the
Formation of Self-Assembled Monolayers on Gold
Frank Buckel,a,1 Per Persson,b,2 Franz Effenberger*a
a Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
Fax +49(711)6854269; E-mail: franz.effenberger@po.uni-stuttgart.de
b Royal Institute of Technology, Department of Organic Chemistry, S-100 44 Stockholm, Sweden
Received 28 December 1998
methyl ether is used as a protecting group which can be
transformed easily in a bromide function.7,8
Abstract: The terminally 2-thienyl- and phenyl-substituted
eicosane derivatives 4 and 5 were prepared by reacting 1-[(20-bro-
moeicosyl)oxy]-4-methoxybenzene (3) with 2-lithiothiophene and
lithium diphenylcuprate, respectively. Reaction of 4 and 5 with
BBr3 leads to the corresponding bromides 6, 7 which afforded the
aryl-substituted eicosanethiols 8 and 9 by nucleophilic substitution
with thiourea. 4-Eicosylthiophenol (13) was prepared from eicosyl-
benzene (11) by chlorosulfonation and subsequent reduction of the
sulfonyl chloride. Synthesis of the thiol 22 with phenylenedioxy
groups incorporated in the alkyl chain involves formation of 19
from allyloxy(bromobutoxy)benzene (18) and (4-(2-thienyl)bu-
toxy)phenol (17). Hydroboration of 19 yields the corresponding al-
cohol 20, which under Mitsunobu conditions and subsequent
reduction with LiAlH4 can be transformed to 22.
Key words: functionalized long-chain alkanethiols, 4-alkyl-
thiophenol, self-assembled monolayers on gold
Long-chain alkanethiols are known to form well ordered
monolayers on gold.3,4 These self-assembled monolayers
(SAMs) are of interest due to their numerous applica-
tions.4 The properties of SAMs (conductivity, wettability
etc.) depend strongly on packing and orientation of the
molecules in the layer. The two-dimensional order results
from intermolecular interactions, e.g. van der Waals inter-
actions. SAMs with aromatic systems incorporated may
act as electron donors or acceptors, and furthermore, the
p-systems could influence the layer structure sterically
and by p-p interaction of the aromatic moiety. Com-
pounds, suitable for formation of SAMs, can be structured
in three parts: an anchor group for linkage to the substrate,
a carbon chain of 2–3 nm length, and a terminal group
with variable chemical functionalities.
Scheme 1
In the present publication we report on the synthesis of
terminally thienyl- and phenyl-substituted alkanethiols, a
4-alkylthiophenol as well as a long-chain thiol with phen-
ylenedioxy groups incorporated in the alkyl chain. The
formation and characterization of SAMs formed from
these adsorbates will be published elsewhere.
Whereas 3 reacted with 2-lithiothiophene9 to give the
w-protected a-(2-thienyl)alkane 4 in 77% yield, the con-
version of 3 with phenyllithium was accompanied by nu-
merous side-reactions.10 The yield of the phenyl
derivative 5 was only 14%. Replacing phenyllithium by
lithium diphenylcuprate10 afforded the coupling product 5
in 80% yield.
BBr3 in boiling dichloromethane8 was found to be more
effective for simultaneous deprotection and bromination
of 4 and 5 than the published system HBr/acetic anhydride
at 100°C.8 In HBr/acetic anhydride compound 6 with ter-
minal thienyl group was isolated in only 42% yield after a
Long-chain alkanethiols can be prepared simply by SN re-
actions from the corresponding alkyl bromides.5 In analo-
gy to a literature-known procedure6 bromide 1 was
converted to the Grignard reagent which was coupled with
1,10-dibromodecane (2) in the presence of a catalytic
amount of Li2CuCl4 to give the a,w-substituted long-chain
alkane 3 (Scheme 1). In bromide 17 hydroquinonemono-
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954
F. Buckel et al.
PAPER
reaction time of 8 d. However, by using BBr3 the w-bro-
mides 6 and 7 were available after 1.5 h in high chemical
yields (Scheme 1). By reaction of 6 and 7 with thiourea in
95% ethanol and cleavage of the resultant isothiouronium
salt with NaOH under argon atmosphere the terminally
aryl-substituted eicosanethiols 8 and 9 were obtained.
In order to compare steric and electronic influences of
alkylthiols with thiophenols as anchor groups for the for-
mation of SAMs on gold, a 4-alkyl substituted thiophenol
of comparable chain length had to be synthesized. The
known eicosylbenzene (11)11 could be prepared by re-
acting 1-bromoeicosane (10) with lithium diphenylcu-
prate (Scheme 2). The thiol function was introduced in the
benzene ring of 11 in the common way5 by chlorosulfona-
tion to sulfonyl chloride 12 and subsequent reduction of
the SO2Cl group with red phosphorus/iodine. The in-
termediate disulfide formed owing to the easy oxidizabil-
ity of thiophenols, could be reduced with zinc in glacial
acetic acid giving 4-eicosylthiophenol (13) in 67% yield.
Scheme 2
The synthetic route to compound 22 with p-phenylene-
dioxy groups incorporated in the alkyl chain, which has
been designed by molecular modelling12 for formation of
SAMs, is based on literature-known methodologies
(Scheme 3).
Scheme 3
level throughout the reaction in order to minimize a
disubstitution of 14. The bromide 18 was prepared by
alkylation of 16 with 1,4-dibromobutane. To avoid di-
alkylation, dibromobutane was added in fivefold excess
(referred to 16). By alkylation of the phenol 17 with bro-
mide 18 compound 19 was obtained in 69% yield (Table
1).
Monoalkylation of hydroquinone (14) with allyl bromide
has been reported to give 16 in only 27% yield after distil-
lation.13 Therefore 16 has been purified by flash chroma-
tography on silica gel. By this procedure the yield could
be improved to 52% (Table 1). Analogously, 14 was re-
acted with bromide 1514 to give 17 in 66% yield (Table 1).
Thereby the concentration of 14 was maintained at a high
Table 1 Synthesis of Compounds 16, 17 and 19
Reaction Conditions
Starting Materials
Prod-
uct
Yield
%
Mp (°C); appearance
14, 17
(mmol)
Bromide
(mmol)
K2CO3
(mmol)
DMF
(mL)
Temp
(°C)
Time
(h)
14
14
17
41.3
114.0
4.18
allyl
15
18
8.6
23.0
4.03
20.6
57.0
4.43
30
60
20
60
80
75
20
4
24
16
17
19
52
66
69
40–42
44–45; pale solid
108–109; white solid
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Synthesis of Functionalized Long-Chain Thiols and Thiophenols
955
13C NMR (CDCl3): d = 26.07–29.93 (CH2), 31.82 (CH2), 55.74
(CH3), 68.68 (CH2O), 114.61 (Ph), 115.43 (Ph), 122.69 (thienyl C-
4), 123.87 (thienyl C-2), 126.62 (thienyl C-3), 145.90 (thienyl C-1),
153.32 (Ph), 153.65 (Ph).
The terminal functionalization of 19 to a thiol was
achieved
by
hydroboration
with
9-borabi-
cyclo[3.3.1]nonane15 (9-BBN) and subsequent oxidation
using H2O2. The regioselectivity of 9-BBN compared
with that of BH3 has been investigated in the transforma-
tion of 18 into the corresponding alcohol: in accordance to
published results,16 the sterically demanding 9-BBN was
found to be significantly more regioselective than BH3
(99.2%: 70%), and therefore it was used as hydroborating
agent for 19. The resulting alcohol 20, which was isolated
in 60% yield, was converted via Mitsunobu reaction with
triphenylphosphine/diethyl azodicarboxylate (DEAD)
and thioacetic acid as a nucleophile to give thioacetate 21
in 79% yield. The synthesis was accomplished by reduc-
tion of the thioacetate with LiAlH4 yielding 86% of the
desired functionalized thiol 22.
Anal. calcd for C31H50O2S: C, 76.49; H, 10.35; S, 6.59. Found: C,
76.48; H, 10.26; S, 6.83.
Preparation of Phenyl-Substituted Compounds 5 and 11; Gen-
eral Procedure
To an ice-cooled suspension of CuBr·Me2S (12 mmol for 3, 40
mmol for 10) in anhyd Et2O (30 or 100 mL) a 1.8 M solution of phe-
nyllithium in cyclohexane/Et2O (2 equiv based on CuBr·MeS) was
added followed by a solution of 3 or 10 in anhyd THF (40 or 25
mL). The mixture was allowed to warm to r.t., and poured onto a so-
lution of NH4Cl . The aqueous phase was extracted several times
with Et2O, and the combined extracts were washed with H2O, dried
(Na2SO4), and concentrated in vacuo.
(20-(4-Methoxyphenoxy)eicosyl)benzene (5)
From 3 (1.45 g, 3.0 mmol), 2.5 d reaction time, chromatography on
silica gel with petroleum ether/CH2Cl2 (1:1) and recrystallization
from MeOH was obtained 1.15 g (80%) of 5 as a colourless solid;
mp 62–63°C.
1H NMR (CDCl3): d = 1.25–1.45 (m, 32 H, 16 CH2), 1.58–1.62 (m,
2 H, CH2), 1.72–1.78 (m, 2 H, CH2), 2.59 (t, J = 7.8 Hz, 2 H,
CH2Ph), 3.76 (s, 3 H, CH3O), 3.90 (t, J = 6.6 Hz, 2 H, OCH2), 6.83
(s, 4 H, Ph), 7.15–7.28 (m, 5 H, Ph).
13C NMR (CDCl3): d = 26.07–29.70 (CH2), 31.54 (CH2), 36.00
(CH2Ph), 55.74 (CH3), 68.68 (CH2O), 114.60 (Ph), 115.43 (Ph),
125.53 (Ph), 128.20 (Ph), 128.39 (Ph), 142.97 (Ph), 153.32 (Ph),
153.65 (Ph).
1H NMR spectra were recorded on a Bruker AC 250 F (250 MHz)
or Bruker ARX 500 (500 MHz) spectrometer with TMS as internal
standard. Mps were determined on a Büchi SMP 20 apparatus and
are uncorrected. Preparative column chromatography was per-
formed using glass columns of different size packed with silica gel
S, grain size 0.032–0.063 mm (Riedel-de Haen). All solvents and
educts were purified and dried. All experiments were carried out un-
der Ar as inert gas in flame-dried apparatus. For reaction yielding
thiols an Oxisorb filter (Messer-Griesheim) was additionally used
and solvents were degassed.
1-[(20-Bromoeicosyl)oxy]-4-methoxybenzene (3)
According to reference 6, from 17 (13.73 g, 40.0 mmol) and 2 (24.01
g, 80.0 mmol); after workup, the excess of 1 was distilled off
(121°C/0.01 Torr), and crude 3 was chromatographed on silica gel
with petroleum ether/CH2Cl2 (1:1); recrystallization from petro-
leum ether/CH2Cl2 gave 3 as colourless crystals (7.07 g, 37%); mp
84°C.
1H NMR (CDCl3): d = 1.26–1.42 (m, 32 H, 16 CH2), 1.69–1.78 (m,
2 H, CH2), 1.82–1.91 (m, 2 H, CH2), 3.41 (t, J = 6.9 Hz, 2 H,
CH2Br), 3.77 (s, 3 H, CH3O), 3.90 (t, J = 6.6 Hz, 2 H, OCH2), 6.83
(s, 4 H, Ph).
Anal. calcd for C33H52O2: C, 82.44; H, 10.90. Found: C, 82.49; H,
11.00.
Eicosylbenzene (11)
From 10 (3.61 g, 10.0 mmol), 1 d reaction time, and fractional dis-
tillation was obtained 2.48 g (69%) of 11 as a colourless solid; bp
175–182°C/0.1 Torr; mp 38–39°C.
1H NMR (CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3), 1.22–1.30 (m,
34 H, 17 CH2), 1.59–1.62 (m, 2 H, CH2), 2.60 (t, J = 7.8 Hz, 2 H,
CH2Ph), 7.15–7.28 (m, 5 H, Ph).
13C NMR (CDCl3): d = 14.13 (CH3), 22.71 (CH2), 29.36–29.71
(CH2), 31.55 (CH2), 31.94 (CH2), 36.01 (CH2Ph), 125.54 (Ph),
128.21 (Ph), 128.40 (Ph), 142.98 (Ph).
13C NMR (CDCl3): d = 26.07–29.69 (CH2), 32.85 (CH2), 34.05
(CH2Br), 55.73 (CH3), 68.66 (CH2O), 114.60 (Ph), 115.41 (Ph),
153.31 (Ph), 153.65 (Ph).
Anal. calcd for C27H47BrO2: C, 67.06; H, 9.80; Br, 16.52. Found: C,
67.28; H, 9.69; Br, 16.37.
Anal. calcd for C26H46: C, 87.07; H, 12.93. Found: C, 87.19; H,
12.95.
2-[20-(4-Methoxyphenoxy)eicosyl]thiophene (4)
Deprotection and Bromination to Compounds 6 and 7; General
Procedure
A solution of 3 (7.0 g, 14.47 mmol) in anhyd THF (180 mL) was
added dropwise at r.t. to a stirred solution of 2-lithiothiophene, pre-
pared from thiophene (2.78 mL, 35.12 mmol) and a 1.6 M solution
of BuLi in hexane (18.1 mL, 28.96 mmol) diluted in THF (21 mL).9
After 3 d, the mixture was hydrolyzed with ice-H2O (70 mL), and
the aqueous phase was extracted several times with Et2O. The com-
bined extracts were dried (Na2SO4), and concentrated in vacuo. The
residue was chromatographed on silica gel with petroleum ether/
CH2Cl2 (1:1). Recrystallization from MeOH gave 4 as yellow crys-
tals (5.44 g, 77%); mp 76°C.
To a solution of 4 or 5 in CH2Cl2 (150 or 10 mL) an equimolar
amount of BBr3 was added dropwise within 5–30 min. After being
refluxed for 1.5 h, the mixture was hydrolyzed with a solution of
NH4Cl, and the aqueous phase was extracted with CH2Cl2 . The
combined extracts were washed with H2O , a solution of NaHCO3
and H2O, dried (Na2SO4), and concentrated in vacuo. The residue
was chromatographed on silica gel with petroleum ether.
2-(20-Bromoeicosyl)thiophene (6)
From 4 (4.87 g, 10.0 mmol) was obtained 3.83 g (86%) of 6 as co-
lourless crystals; mp 42–43°C.
1H NMR (CDCl3): d = 1.25–1.45 (m, 32 H, 16 CH2), 1.61–1.70 (m,
2 H, CH2), 1.79–1.91 (m, 2 H, CH2), 2.81 (t, J = 7.6 Hz, 2 H, CH2),
3.40 (t, J = 6.9 Hz, 2 H, CH2Br), 6.77 (dd, J = 3.4, 1.0 Hz, 1 H, thie-
1H NMR (CDCl3): d = 1.25–1.43 (m, 32 H, 16 CH2), 1.61–1.80 (m,
4 H, 2 CH2), 2.81 (t, J = 7.5 Hz, 2 H, CH2), 3.76 (s, 3 H, CH3O), 3.89
(t, J = 6.6 Hz, 2 H, OCH2), 6.77 (dd, J = 3.4, 1.0 Hz, 1 H, thienyl H-
3), 6.83 (s, 4 H, Ph), 6.91 (dd, J = 5.1, 3.4 Hz, 1 H, thienyl H-4),
7.09 (dd, J = 5.1, 1.1 Hz, 1 H, thienyl H-5).
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956
F. Buckel et al.
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nyl H-3), 6.91 (dd, J = 3.4, 5.1 Hz, 1 H, thienyl H-4), 7.10 (dd, J =
5.1, 1.1 Hz, 1 H, thienyl H-5).
13C NMR (CDCl3): d = 28.20–29.93 (CH2), 31.82 (CH2), 32.86
(CH2), 34.04 (CH2Br), 122.69 (thienyl C-4), 123.87 (thienyl C-2),
126.62 (thienyl C-3), 142.89 (thienyl C-1).
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H, CH3), 1.25–1.32 (m,
34 H, 17 CH2), 1.63–1.66 (m, 2 H, CH2), 2.72 (t, J = 7.8 Hz, 2 H,
CH2Ph), 7.40 (d, J = 8.5 Hz, 2 H, Ph), 7.94 (d, J = 8.5 Hz, 2 H, Ph).
13C NMR (CDCl3): d = 14.13 (CH3), 22.70 (CH2), 29.20–29.71
(CH2), 30.95 (CH2), 31.93 (CH2), 36.07 (CH2Ph), 127.09 (Ph),
129.59 (Ph), 141.77 (Ph), 151.68 (Ph).
Anal. calcd for C24H43BrS: C, 64.98; H, 9.77; Br, 18.01; S, 7.23.
Found: C, 64.77; H, 9.84; Br, 18.22; S, 7.19.
Anal. calcd for C26H45ClO2S: C, 68.31; H, 9.92; Cl, 7.76; S, 7.01.
Found: C, 68.51; H, 10.00; Cl, 7.60; S, 6.76.
20-Bromoeicosylbenzene (7)
From 5 (961.5 mg, 2.0 mmol) was obtained 766.9 mg (88%) of 7 as
a colourless solid; mp 36°C.
1H NMR (CDCl3): d = 1.25–1.43 (m, 32 H, 16 CH2), 1.57–1.62 (m,
2 H, CH2), 1.82–1.88 (m, 2 H, CH2), 2.59 (t, J = 7.8 Hz, 2 H,
CH2Ph), 3.40 (t, J = 6.9 Hz, 2 H, CH2Br), 7.15–7.28 (m, 5 H, Ph).
13C NMR (CDCl3): d = 28.19–29.69 (CH2), 31.55 (CH2), 32.85
(CH2), 34.08 (CH2Br), 36.00 (CH2Ph), 125.53 (Ph), 128.20 (Ph),
128.39 (Ph), 142.96 (Ph).
4-Eicosylthiophenol (13)
To a boiling suspension of red phosphorus (83.6 mg, 2.7 mmol) and
iodine (4.1 mg, 0.016 mmol) in glacial HOAc (7 mL) 12 (457.2 mg,
1.0 mmol) was added portionwise within 15 min. After being heated
to reflux for 23 h, H2O (1 mL) was added, and the mixture refluxed
for a further 1 h. Then CH2Cl2 and H2O were added, and the aque-
ous phase extracted with CH2Cl2. The combined extracts were
washed with H2O, dried (Na2SO4), and concentrated in vacuo. The
residue was chromatographed on silica gel with petroleum ether to
give 303.3 mg (78%) of disulfide.
Anal. calcd for C26H45Br: C, 71.37; H, 10.37; Br, 18.26. Found: C,
71.47; H, 10.40; Br, 17.98.
To a solution of disulfide (288.0 mg, 0.37 mmol) in CH2Cl2 (20 mL)
Zn dust (196.1 mg, 3.0 mmol) and glacial HOAc (0.5 mL) were add-
ed. After stirring for 15 h, the mixture was filtered through a silica
gel column. The resulting solid was recrystallized from MeOH to
give 13 as a colourless solid (246.9 mg, 86%); mp 54–55°C.
1H NMR (CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3), 1.21–1.29 (m,
34 H, 17 CH2), 1.55–1.58 (m, 2 H, CH2), 2.54 (t, J = 7.7 Hz, 2 H,
CH2Ph), 3.38 (s, 1 H, SH), 7.05 (d, J = 8.1 Hz, 2 H, Ph), 7.20 (d, J
= 8.1 Hz, 2 H, Ph).
Preparation of Thiols 8 and 9; General Procedure
A solution of 6 or 7 and thiourea (1.1 equiv) in EtOH (95%) was
heated to reflux for 20 h. Then 5 M NaOH (1.2 or 0.6 mL) was add-
ed, and the mixture was refluxed for a further 4 h. After being
cooled to r.t., CH2Cl2 and H2O were added. The aqueous phase was
extracted with CH2Cl2 . The combined extracts were washed with
H2O, a solution of NH4Cl and H2O , dried (Na2SO4), and concentrat-
ed in vacuo. The residue was chromatographed on silica gel with pe-
troleum ether/CH2Cl2 (10:1) (8) or petroleum ether (9).
13C NMR (CDCl3): d = 14.14 (CH3), 22.71 (CH2), 29.23–29.71
(CH2), 31.44 (CH2), 31.94 (CH2), 35.40 (CH2Ph), 126.76 (Ph),
129.20 (Ph), 129.86 (Ph), 140.79 (Ph).
20-(2-Thienyl)eicosanethiol (8)
From 6 (887.1 mg, 2.0 mmol) was obtained 623.2 mg (79%) of 8 as
a colourless solid; mp 45–46°C.
Anal. calcd for C26H46S: C, 79.93; H, 11.87; S, 8.21. Found: C,
79.99; H, 11.98; S, 8.16.
1H NMR (CDCl3): d = 1.25–1.36 (m, 32 H, 16 CH2), 1.33 (t, J = 7.7
Hz, 1 H, SH), 1.58–1.70 (m, 4 H, CH2), 2.48–2.56 (m, 2 H, CH2SH),
2.81 (t, J = 7.6 Hz, 2 H, CH2), 6.77 (dd, J = 3.4, 0.8 Hz, 1 H, thienyl
H-3), 6.91 (dd, J = 5.1, 3.4 Hz, 1 H, thienyl H-4), 7.10 (dd, J = 5.1,
1.1 Hz, 1 H, thienyl H-5).
13C NMR (CDCl3): d = 24.68 (CH2SH), 28.40–29.93 (CH2), 31.82
(CH2), 34.07 (CH2), 122.70 (thienyl C-4), 123.87 (thienyl C-2),
126.62 (thienyl C-3), 145.90 (thienyl C-1).
Preparation of Compounds 16, 17 and 19; General Procedure
To a stirred solution of 14 and potassium carbonate in anhyd DMF
under Ar allyl bromide or a solution of 1514 in DMF (10 mL) was
added dropwise over 0.5–1 h. In the case of 19, K2CO3 was added
to a stirred solution of 18 and 17 in anhyd DMF (20 mL). After heat-
ing to 60–80°C (Table 1), the mixture was allowed to cool to r.t., hy-
drolyzed with ice–H2O, and neutralized in the case of 16, 17 with 1–
2 M HCl. Then it was extracted with CH2Cl2. The combined ex-
tracts were washed with H2O, dried (Na2SO4), and concentrated in
vacuo. The residue was chromatographed on silica gel with CH2Cl2
or 2% MeOH in CH2Cl2 (for 17) (Table 1 and 2).
Anal. calcd for C24H44S2: C, 72.66; H, 11.18; S, 16.16. Found: C,
72.67; H, 11.25; S, 16.29.
20-Phenyleicosanethiol (9)
From 7 (437.6 mg, 1.0 mmol) was obtained 245.7 mg (63%) of 9 as
a colourless solid; mp 40–41°C.
1H NMR (CDCl3): d = 1.25–1.38 (m, 32 H, 16 CH2), 1.33 (t, J = 7.7
Hz, 1 H, SH), 1.57–1.63 (m, 4 H, CH2), 2.50–2.54 (m, 2 H, CH2SH),
2.60 (t, J = 7.8 Hz, 2 H, CH2Ph), 7.15–7.29 (m, 5 H, Ph).
13C NMR (CDCl3): d = 24.67 (CH2SH), 28.39–29.69 (CH2), 31.54
(CH2), 34.07 (CH2), 36.00 (CH2Ph), 125.53 (Ph), 128.20 (Ph),
128.39 (Ph), 142.97 (Ph).
Allyloxy-4-(4-bromobutoxy)benzene (18)
To a vigorously stirred solution of 16 (5.38 g, 36.0 mmol) and 1,4-
dibromobutane (39.0 g, 180.0 mmol) in MeOH (30 mL) at 60°C un-
der Ar was added dropwise a solution of KOH (2.02 g, 36.0 mmol)
in MeOH (20 mL) within 3 h. After being refluxed for a further 6 h,
the mixture was allowed to cool to r.t., mixed with ice–H2O (300
mL) and left for 0.5 h. Then it was neutralized with dilute HCl and
extracted with CH2Cl2 (3 x 150 mL each). The combined extracts
were washed with H2O, dried (Na2SO4), and concentrated. The res-
idue was chromatographed on silica gel with CH2Cl2. In order to re-
move dibromobutane completely, the remaining oil was distilled
bulb-to-bulb at 40°C/0.2 Torr to give 18 as a white solid (6.57 g,
64%); mp 34°C.
Anal. calcd for C26H46S: C, 79.92; H, 11.87; S, 8.21. Found: C,
79.77; H, 11.88; S, 8.35.
4-Eicosylbenzenesulfonyl Chloride (12)
To a solution of 11 (1.79 g, 5.0 mmol) in CHCl3 (5 mL) chlorosul-
furic acid (1 mL, 15.0 mmol) was added, and the mixture was stirred
at r.t. for 22 h. Then it was poured on ice, and the aqueous phase was
extracted with CH2Cl2 . The combined extracts were washed with
H2O, a solution of NaHCO3 and H2O, dried (Na2SO4), and concen-
trated in vacuo. The residue was chromatographed on silica gel with
petroleum ether/CH2Cl2 (3:1) to give 12 as a colourless solid (1.67
g, 73%); mp 59°C.
1H NMR (CDCl3): d = 1.85–2.12 (m, 4 H, 2 CH2), 3.48 (t, J = 6.5
Hz, 2 H, CH2Br), 3.94 (t, J = 5.9 Hz, 2 H, OCH2), 4.46–4.50 (m, 2
H, =CHCH2), 5.24–5.44 (m, 2 H, CH2=), 5.97–6.12 (m, 1 H, =CH),
6.78–6.87 (m, 4 H, Ph).
Synthesis 1999, No. 6, 953–958 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Long-Chain Thiols and Thiophenols
957
13C NMR (CDCl3): d = 28.0, 29.5 (CH2), 33.5 (CH2Br), 67.4
(OCH2), 69.5 (=CHCH2), 115.3, 115.7 (Ph), 117.5 (CH2=), 133.6
(CH), 152.8, 153.2 (Ph).
was added dropwise within 20 min. After stirring at 0°C for a fur-
ther 1 h, the mixture was allowed to warm to r.t. (17 h). The reaction
was terminated by concentration in vacuo. The residue was chro-
matographed on silica gel with CH2Cl2 to give 21 as a colourless
solid (207.4 mg, 79%); mp 102–104°C (Table 2).
Anal. calcd for C13H17BrO2: C, 54.75; H, 6.01; Br, 28.02. Found: C,
54.90; H, 5.95; Br, 27.98.
3-[4-(4-{4-[4-(2-Thienyl)butoxy]phenoxy}butoxy)phenoxy]-1-
propanethiol (22)
3-[4-(4-{4-[4-(2-Thienyl)butoxy]phenoxy}butoxy)phenoxy]-1-
propanol (20)
To a solution of 21 (158.6 mg, 0.3 mmol) in anhyd THF (5 mL) at
r.t. was added LiAlH4 (22.8 mg, 0.6 mmol), and the mixture was
stirred for 2 h. After addition of 1 M HCl (5 mL) followed by
CH2Cl2 (10 mL) (ice-cooling) and 1 M HCl (5 mL) at r.t., the mix-
ture was stirred for 0.5 h. The phases were separated, and the aque-
ous phase was extracted three times with CH2Cl2. The combined
extracts were washed with H2O, dried (Na2SO4), and concentrated
in vacuo. The residue was chromatographed on silica gel with
CH2Cl2 to give 22 as a colourless solid (125.0 mg, 86%); mp 105–
106°C (Table 2).
To a solution of 19 (1.58 g, 3.49 mmol) in anhyd THF (25 mL) un-
der N2 a 0.5 M solution of 9-borabicyclo[3.3.1]nonane (9-BBN) in
THF (9.0 mL, 4.50 mmol) was slowly added, and the mixture was
heated to reflux for 6 h. After being allowed to cool to r.t., a mixture
from 30% solution of H2O2 (2 mL, 17.0 mmol) and 5 M solution of
KOH (4 mL, 20.0 mmol) was added. The mixture was heated to
50°C for 1.5 h, and stirred for a further 15 h. The precipitate was fil-
tered off, and washed with a small volume of cold THF and H2O.
Recrystallization from THF and flash chromatography on silica gel
with 2% MeOH in CH2Cl2 gave 20 as a white solid (979 mg, 60%);
mp 128–129°C (Table 2).
Acknowledgement
S-3-[4-(4-{4-[4-(2-Thienyl)butoxy]phenoxy}butoxy)phe-
noxy]propyl Thioacetate (21)
To a solution of PPh3 (262.3 mg, 1.0 mmol) in anhyd THF (5 mL)
at 0°C was added dropwise DEAD (156 mL, 1.0 mmol), and the
mixture was stirred for 0.5 h. Then a solution of 20 (235.3 mg, 0.5
mmol) and thioacetic acid (71 mL, 1.0 mmol) in anhyd THF (30 mL)
Acknowledgement is made to Prof. C. Moberg (Royal Institute of
Technology, Department of Organic Chemistry, S-100 44 Stock-
holm, Sweden) for accepting the role as examiner for the "examens-
arbete" of P. Persson. We would like to thank Dr. A. Baro for
translating and revising the manuscript.
Table 2 Spectroscopic Data of Compounds 17, and 19–22
Prod-
uctb
1H NMR (500 MHz, CDCl3/TMS)
d, J (Hz)
13C NMR (CDCl3/TMS)
d
17
1.81–1.88 (m, 4 H, CH2), 2.89 (t, J = 6.9, 2 H, CH2), 3.91 (t,
J = 6.0, 2 H, OCH2), 4.60 (s, 1 H, OH), 6.73–6.78 (m, 4 H, Ph),
6.80 (dd, J = 1.1, 3.4, 1 H, thienyl H-3), 6.91 (dd, J = 3.4, 5.1,
1 H, thienyl H-4), 7.11 (dd, J = 1.2, 5.1, 1 H, thienyl H-5)
28.3, 28.7 (CH2), 29.6 (CH2), 68.3 (OCH2), 115.6, 116.0 (Ph),
123.0 (thienyl C-4), 124.2 (thienyl C-2), 126.7 (thienyl C-3),
145.1 (thienyl C-1), 149.4 (Ph C-1), 153.2 (Ph C-4)
19
1.80–1.87 (m, 4 H, CH2), 1.91–1.96 (m, 4 H, CH2), 2.90 (t, J =
6.9, 2 H, CH2), 3.92 (t, J = 5.9, 2 H, OCH2), 3.97 (t, J = 5.5,
4 H, 2 OCH2), 4.47–4.49 (m, 2 H, =CHCH2), 5.25–5.41 (m,
2 H, CH2=), 6.00–6.08 (m, 1H, CH), 6.77-6.87 (m, 9 H, Ph,
thienyl H-3), 6.91 (dd, J = 3.5, 5.1, 1 H, thienyl H-4), 7.11 (dd,
J = 1.1, 5.1, 1 H, thienyl H-5)
26.5 (CH2), 28.7, 29.2 (CH2), 30.0 (CH2), 68.5, 68.6, 69.9
(CH2O), 115.8, 116.1 (Ph), 117.9 (CH2=), 123.4 (thienyl C-4),
124.6 (thienyl C-2), 127.1 (thienyl C-3), 134.0 (CH), 145.5
(thienyl C-1), 153.1 (Ph C-4), 153.5, 153.6, 153.7 (Ph C-1,4)
20a
21
1.73–1.78 (m, 4 H, CH2), 1.78–1.84 (m, 6 H, CH2), 2.85 (t, J =
6.8, 2 H, CH2), 3.52-3.55 (m, 2 H, CH2OH), 3.90–3.96 (m,
8 H, CH2O), 4.52 (t, J = 5.1, 1 H, OH), 6.82–6.88 (m, 9 H, Ph,
thienyl H-3), 6.93 (dd, J = 3.4, 5.0, 1 H, thienyl H-4), 7.31 (dd,
J = 0.8, 5.1, 1 H, thienyl H-5)
25.4 (CH2), 27.8, 28.1, 28.7 (CH2), 32.1 (CH2), 57.2 (CH2OH),
64.8, 67.4 (CH2O), 115.1, 115.2 (Ph), 123.3 (thienyl C-4),
124.3 (thienyl C-2), 126.8 (thienyl C-3), 144.5 (thienyl C-1),
152.4, 152.5, 152.6 (Ph C-1,4)
1.82–1.89 (m, 4 H, CH2), 1.92–1.96 (m, 4 H, CH2), 2.04 (tt,
J = 6.1, 7.1, 2 H, CH2), 2.34 (s, 3 H, CH3), 2.90 (t, J = 7.0,
2 H, CH2), 3.05 (t, J = 7.1, 2 H, SCH2), 3.93 (t, J = 6.1, 2 H,
OCH2), 3.96 (t, J = 6.1, 4 H, CH2O), 3.97 (t, J = 5.9, 2 H,
CH2O), 6.80 (dd, J = 1.0, 3.4, 1 H, thienyl H-3), 6.82 (s, 8 H,
Ph), 6.92 (dd, J = 3.4, 5.1, 1 H, thienyl H-4), 7.12 (dd, J = 1.1,
5.1, 1 H, thienyl H-5)
25.92-29.62 (CH2), 30.65 (CH3), 66.85, 68.11, 68.20 (CH2O),
115.40, 115.47 (Ph), 122.95 (thienyl C-4), 124.18 (thienyl
C-2), 126.70 (thienyl C-3), 145.11 (thienyl C-1), 152.90,
153.11, 153.17, 153.28 (Ph C-1,4), 195.81 (C=O)
22
1.39 (t, J = 8.1, 1 H, SH), 1.81–1.89 (m, 4 H, CH2), 1.93–1.96
(m, 4 H, CH2), 2.05 (tt, J = 7.1, 5.9, 2 H, CH2), 2.73 (td, J =
6.9, 8.2, 2 H, CH2SH), 2.90 (t, J = 6.9, 2 H, CH2), 3.93 (t, J =
6.0, 2 H, OCH2), 3.97 (t, J = 5.4, 4 H, CH2O), 4.02 (t, J = 5.9,
2 H, CH2O), 6.80 (dd, J = 1.1, 3.4, 1 H, thienyl H-3), 6.82, 6.83
(each s, 8 H, Ph), 6.92 (dd, J = 3.4, 5.1, 1 H, thienyl H-4), 7.12
(dd, J = 1.0, 5.1, 1 H, thienyl H-5)
21.31 (CH2SH), 26.10-29.62 (CH2), 33.46 (CH2), 66.28,
68.12, 68.21 (CH2O), 115.41, 115.44 (Ph), 122.96 (thienyl
C-4), 124.19 (thienyl C-2), 126.71 (thienyl C-3), 145.12
(thienyl C-1), 152.95, 153.11, 153.17, 153.27 (Ph C-1,4)
a In DMSO-d6.
b Satisfactory microanalysis found for each compound.
Synthesis 1999, No. 6, 953–958 ISSN 0039-7881 © Thieme Stuttgart · New York

958
F. Buckel et al.
PAPER
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Synthesis 1999, No. 6, 953–958 ISSN 0039-7881 © Thieme Stuttgart · New York