Efficient preparation of novel phenolic surfactants for self-assembled monolayers

Article abstract of DOI:10.1080/00397911.2013.844259

Novel molecules have been synthesized that combine the phenolic nature of tannins and self-assembling properties of surfactants. These single-chain (C₁₂) surfactants with potential biocompatibility have been synthesized with an ω-thiol or disulfide functionality, both commonly used anchors in self-assembly onto gold surfaces, using a modular route. Protecting groups for the phenol and thiol moieties played a key role for overcoming the challenges often associated with the purification of surfactants. The tasks of unmasking the thiol moiety and simultaneously deprotecting the acetyl protecting groups of the phenols were accomplished using sodium thiomethoxide. This modular route can be extended to synthesize other surfactants with the potential ability to form robust layers with biocompatible properties.

Full text of DOI:10.1080/00397911.2013.844259

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Efficient Preparation of Novel Phenolic
Surfactants for Self-Assembled
Monolayers
Arison Rajasingam a , Rolf Schmidt a , Simon Woo a , Christine
DeWolf a & Pat Forgione a
a Department of Chemistry and Biochemistry , Centre for
NanoScience Research, Concordia University , Montreal , Canada
Accepted author version posted online: 08 Nov 2013.Published
online: 19 Mar 2014.
To cite this article: Arison Rajasingam , Rolf Schmidt , Simon Woo , Christine DeWolf & Pat Forgione
(2014) Efficient Preparation of Novel Phenolic Surfactants for Self-Assembled Monolayers, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:8, 1066-1075, DOI: 10.1080/00397911.2013.844259
To link to this article: http://dx.doi.org/10.1080/00397911.2013.844259
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Synthetic Communications1, 44: 1066–1075, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.844259
EFFICIENT PREPARATION OF NOVEL PHENOLIC
SURFACTANTS FOR SELF-ASSEMBLED MONOLAYERS
Arison Rajasingam, Rolf Schmidt, Simon Woo,
Christine DeWolf, and Pat Forgione
Department of Chemistry and Biochemistry, Centre for NanoScience
Research, Concordia University, Montreal, Canada
GRAPHICAL ABSTRACT
Abstract Novel molecules have been synthesized that combine the phenolic nature of tannins
and self-assembling properties of surfactants. These single-chain (C12) surfactants with
potential biocompatibility have been synthesized with an x-thiol or disulfide functionality,
both commonly used anchors in self-assembly onto gold surfaces, using a modular route.
Protecting groups for the phenol and thiol moieties played a key role for overcoming the
challenges often associated with the purification of surfactants. The tasks of unmasking
the thiol moiety and simultaneously deprotecting the acetyl protecting groups of the phenols
were accomplished using sodium thiomethoxide. This modular route can be extended to syn-
thesize other surfactants with the potential ability to form robust layers with biocompatible
properties.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Deprotection; disulfides; sodium thiomethoxide; surfactants; tannins; thiols
INTRODUCTION
Surfactants are an important class of molecules that can be used for a variety of
applications. Films formed using surfactants have found applications as protective
coatings,[1] models to study protein adsorption on varied surfaces,[2] and fabrication
Received June 25, 2013.
Address correspondence to Pat Forgione, Concordia University, Chemistry and Biochemistry,
7141 Sherbrooke Street West SP 275.11, Montreal, QC, H4B 1R6, Canada. E-mail: Pat.Forgione@
concordia.ca
1066

NOVEL PHENOLIC SURFACTANTS
1067
of microarrayed chips.[3] The antioxidant and protein binding abilities of tannins[4]
(Fig. 1), when combined with the film-forming capabilities of surfactants, present
potential applications for these novel surfactants as biosensors,[5] coatings,[6] and
immobilized phases in column chromatography.[7] Tannins are a class of
polyphenol-derived compounds commonly found in plants, fruits,[8] and alcoholic
beverages.[9] Some of the reported benefits of high tannin content in food include
the apoptosis of cancerous cells[10] and the prevention of cardiovascular disease.[11]
Our focus is to create tannin-like films that can confer biocompatibility and
protein-binding abilities to a surface. We designed novel surfactants (Fig. 2) combin-
ing tannin-based head groups and a hydrophobic spacer with either x-thiols or
terminal disulfides to produce monolayer films chemisorbed onto gold surfaces.
These molecules exploit the ease of self-assembly and the strength of the Au-S bond.
Both thiols and disulfides, although structurally different, have been shown to form
alkyl thiolate self-assembled monolayers (SAMs) at the gold surface.[12] Further-
more, film properties such as film thickness, wettability, and rate of formation were
independent of the oxidation state of the sulfur terminus of the surfactant.[12]
A
variety of functionalities, including different phenolic moieties, can be introduced
at the head group to control the exposed surface of the monolayer.[13]
C16 aliphatic surfactants with mono-, di-, and tri-hydroxyl substituted aromatic
rings have been synthesized exclusively without x- thiol functionality via direct esteri-
fication.[14] The synthesis of related surfactants has also been accomplished through
N,N0-dicyclohexylcarbodiimide (DCC)–activated esterification of an aliphatic alco-
hol with the corresponding carboxylic acid.[15–17] Other synthetic routes involve the
use of catalytic Pd[18] or acidic functional ionic liquids.[19] Once the long hydrocarbon
chain of the alcohol is incorporated into the surfactant molecule, the chromato-
graphic behavior of the alcohol and the esterification product is often similar. In cases
where the esterification is incomplete, purification of the product can be challenging
because of co-elution of the esterification product with any unreacted aliphatic
alcohol during chromatography. As a result, alternative routes were investigated that
would overcome these limitations, namely a strategy where the galloyl moiety would
be protected to facilitate purification of the intermediates. This approach still
required a method to introduce the x- thiol group, and we needed to consider the
Figure 1. Naturally occurring tannins. (Figure is provided in color online.)

1068
A. RAJASINGAM ET AL.
Figure 2. Novel phenolic surfactants. (Figure is provided in color online.)
chemoselectivity of reactions subsequent to the esterification reaction to maintain the
integrity of the internal ester linkage. The hydroxyl groups of the gallic acid moiety
are often protected using acetyl[20] and benzoyl groups.[21] This modification is used
to accommodate multistep synthesis where the hydroxyl groups may interfere
with the transformations required during the synthesis. The polarity of the gallic
acid moiety is also reduced, facilitating purification by normal phase column
chromatography.
The other consideration is the x-functionalization for gold–thiol chemistry and
chemisorbed films. Organic thiosulfates have found wide use in self-assembly, as an
Au-S bond forms as a result of the cleavage of an S-SO3 bond at the gold surface.
Preparation of the thiosulfate salt is required for this route that may add unnecessary
complication to the synthesis.[22] Syntheses of thiol functionalized amphiphiles have
been accomplished through nucleophilic substitution with hexamethyldisilathianes in
the presence of tetrabutylammonium fluoride.[23] A general route to introduce
x-thiol groups involves the deprotection of thioacetates. This method appeared to
be more suited to our needs because the thioacetate group could be introduced into
our surfactant molecule through an SN2 displacement reaction on an appropriate
intermediate.[24]
Conditions for the removal of the protecting groups, once they have served
their purpose, also needed to be considered. Previously used modes of acetyl depro-
tection include costly metals such as palladium.[21] Another, more cost-effective
route was described using ammonium acetate, providing selective deprotection under
neutral conditions. However, it has not been demonstrated in the presence of thioa-
cetates.[25] Thioacetates have been deprotected using sodium thiomethoxide[25] and
tertbutylammonium cyanide.[26] The procedure using tertbutylammonium cyanide
allows for the deprotection of thioacetates in the presence of an acetate group but
is not exclusively selective for the deprotection of thioacetates, whereas sodium
thiomethoxide is reported to have better selectivity. Thus, the timing of and the con-
ditions used for the deprotection step(s) in the sequence would have to be considered
carefully to avoid potential issues with a lack of chemoselectivity. Possible oxidation

NOVEL PHENOLIC SURFACTANTS
1069
of the deprotected thiol to the corresponding disulfide was only a minor concern
because, as mentioned previously, both species can be used to produce gold-thiolate
SAMs. Above all, however, the deprotection steps must not cleave the internal ester.
The resulting novel surfactants will be further analyzed as self-assembled monolayers
for possible tannin-like properties, and these studies will be reported elsewhere in
due course.
RESULTS AND DISCUSSION
The initial esterification of the proposed modular route was accomplished via
an acid chloride (2A) prepared from the corresponding carboxylic acid[27] (Table 1).
Initial results employing a 1:1 ratio of acid chloride (2A)–alcohol provided the cor-
responding bromide product (3A) in 56% yield. However, a significant amount of
unreacted alcohol remained that rendered the subsequent purification challenging
(entry 1). Increasing the amount of the acid chloride (2A) employed to 1.25 equiva-
lents both increased the yield to 72% and simplified the purification process (entry 2).
These conditions were then also applied for the preparation of the protected
mono-hydroxy bromide (3B, entry 3) from the corresponding acid chloride (2B).
The subsequent SN2 substitution of thioacetate on the alkyl bromide (3A) was
then investigated[24] (Table 2). Initial attempts employing a 1:1 ratio of the bromi-
nated starting material (3A) and potassium thioacetate at room temperature proved
unsuccessful, yielding a complex mixture (entry 1). When the reaction was conducted
starting at a lower temperature, however, the corresponding thioacetate product was
obtained in a 78% yield for the triacetylated compound (4A, entry 2) and 69% yield
for the monoacetylated analog (4B, entry 3).
The key deprotection of the thioacetate (4) to produce the corresponding thiol
or disulfide (1) in the presence of the internal ester was subsequently examined[25]
(Table 3). Initial attempts employing a 1:1 ratio of sodium thiomethoxide to thioe-
ster at 23 ꢀC proved to be unsuccessful (entry 1), producing a mixture of unidentified
Table 1. Effect of equivalents of acid chloride on esterification
Entry
Compound
Equivalents acid chloride
Equivalents bromododecanol
Yield (%)
1
2
3
3A
3A
3B
1.0
1.0
1.0
1.0
56
72
63
1.25
1.25

1070
A. RAJASINGAM ET AL.
Scheme 1. Efficient preparation of amphiphilic surfactant. (Figure is provided in color online.)
products. In contrast, when the starting reaction temperature was lowered, the
sodium thiomethoxide deprotected the thioacetate to form the corresponding thiol
but also displayed a unique ability to simultaneously deprotect the phenolic acetates
(Table 3). The transformation provided yields of 53% for the trihydroxy (1A, entry 2)
and 36% for the monohydroxy (1B, entry 3) products. The cleavage of the phenolic
acetates, while welcome, was somewhat surprising because Wallace and Springer had
reported that esters were stable to these reaction conditions, and had even reported
an example of the cleavage of a thioacetate in the presence of acetates of primary and
secondary alcohols.[25] The fact that the internal ester remained intact is in accord
with their observations, and suggests that the cleavage of the phenolic acetates
may be a reflection of the greater stability of a phenol as a leaving group compared
to an aliphatic alcohol. Cleavage of phenolic acetates has been previously observed
in mildly basic methanol,[28,29] which may indicate that the deprotection of the
Table 2. Synthesis of thioesters from bromide
Entry
Compound
T (ꢀC)
Yield (%)
1
2
3
4A
4A
4B
23
ꢁ78 to 23
ꢁ78 to 23
—
78
69

NOVEL PHENOLIC SURFACTANTS
1071
Table 3. Simultaneous deprotection of acetyl protecting groups and thioacetate of amphiphilic surfactant
Entry
Compound
T (ꢀC)
Yield (%)
1
2
3
1A
1A
1B
23
ꢁ78 to 23
ꢁ78 to 23
—
53
36
phenolic acetates in our reaction is a consequence of the mildly basic methanolic
reaction conditions produced by the sodium thiomethoxide. Regardless, this double
deprotection employing sodium thiomethoxide presented an ideal route, as the thiol
and hydroxyl groups on the aromatic ring were unmasked while a key internal ester
linkage was maintained that facilitated the synthesis of these surfactants. Interest-
ingly, while the monohydroxy analog was isolated as the free thiol, the trihydroxy
analog was more susceptible to air oxidation and was isolated as the disulfide.
The reason for this difference is not clear but is inconsequential for our purposes,
as both can be used to create the desired thiolate–gold surfaces.
In summary, a novel di-deprotection strategy has been employed to synthesize
a novel class of surfactants. The most commonly faced challenges in the preparation
of surfactants involve the polarity of the molecules and the ability to remove impu-
rities that tend to co-elute with the desired product, both of which were surmounted
in this route by the judicious use of protecting groups. By delaying the deprotection
steps until the end of the synthesis, the chemoselectivity of thioacetate over acetate
cleavage was overcome by employing a single reagent to simultaneously remove both
these protecting groups to produce the desired surfactants in good yield. The use of
sodium thiomethoxide in a di-deprotection strategy as demonstrated herein could be
applied to a range of related surfactants. The novel surfactants synthesized have
been further analyzed as self-assembled monolayers for possible tannin-like proper-
ties, and these results will be presented in due course.
EXPERIMENTAL
General Procedure for the Synthesis of Acetylated Compounds
Acetic anhydride (5.8 equiv) was added to hydroxyl substituted benzoic acid
(1.0 equiv) followed by the addition of sulfuric acid (0.058 equiv) dropwise.[20] The
solution was stirred for 1 h. Water (0.19 equiv) was then added to the reaction

1072
A. RAJASINGAM ET AL.
mixture and allowed to stir for 3 h. The contents were then transferred to a separa-
tory funnel and extracted with ethyl acetate (10 ꢂ 10 mL). The combined organic
layers were dried with Na2SO4 and filtered through cotton. The resulting mixture
was concentrated under reduced pressure to provide the corresponding product.
3,4,5-Triacetoxybenzoic Acid
1
White solid, yield 1.50 g (84%), limiting reagent: gallic acid: 6 mmol; H NMR
(CDCl3, 500 MHz): d ppm 7.84 (s, 2H, ArH), 2.30 (s, 9H, OAc)
Characterization details previously reported[30] (CAS 6635-24-1).
General Procedure for the Synthesis of Compounds 2A–2B
Thionyl chloride (3 equiv) was added to acetylated reactant (1 equiv) in ben-
zene (0.5 M), and the reaction mixture was then heated at reflux for 2 h.[27] The
resulting mixture was concentrated under reduced pressure.
[31]
3,4,5-Tris(acetyloxy)-benzoyl Chloride (2A) (CAS 70475-59-1)
Yellowish white solid, crude product used, limiting reagent: 3,4,5-triacetoxy-
1
benzoic acid: 1 mol; H NMR (CDCl3, 500 MHz): d ppm 7.84 (s, 2H, ArH), 2.30
(s, 9H, OAc).
General Procedure for the Synthesis of Compounds 3A–3B
12-Bromododecanol (1 equiv) was added to a solution of 2 (1.25 equiv) in
tetrahydrofuran (THF) (0.1 M), followed by triethylamine (1.25 equiv), and the
reaction mixture was stirred at room temperature for 48 h. Ethyl acetate was used
to transfer the contents to a separatory funnel. The organic layer was washed with
ammonium chloride (0.1 M) (5 ꢂ 10 mL). The combined aqueous layers were
extracted with ethyl acetate (2 ꢂ 20 mL). The combined organic layers were dried
with Na2SO4 and filtered through cotton. The resulting mixture was concentrated
under reduced pressure. The crude product was purified by silica-gel column
chromatography, eluting with mixtures of hexane and ethyl acetate.
5-((12-Bromododecyloxy)carbonyl)benzene-1,2,3-triyl triacetate
(3A). White solid, yield 1.91 g (72%), limiting reagent: 12-bromododecanol
4.8 mmol; mp 68–69 ꢀC; IR: 2921, 2850, 1776, 1723, 1594, 1493, 1470, 1427, 1374,
1
1326, 1244, 1186, 1056, 1017, 903, 849, 782, 766, 721, 642, 430 cmꢁ1. H NMR
(CDCl3, 500 MHz): d ppm 7.78 (s, 2 H, ArH), 4.29 (t, 2 H, J ¼ 7.0 Hz, CO2CH2),
3.40 (t, 2 H, J ¼ 7.0 Hz, Br-CH2), 2.29 (s, 9 H, OAc), 1.84 (q, 2 H, J ¼ 7.0 Hz,
CH2), 1.71 (q, 2 H, J ¼ 7.5 Hz, CH2), 1.30 (m, 16 H, CH2); 13C NMR (CDCl3,
125 MHz): d ppm 167.6, 166.4, 164.4, 143.3, 138.5, 128.7, 122.1, 65.7, 34.0, 32.8,
29.4, 29.2, 28.1, 25.8, 20.5, 20.1; ESI MS: calcd. C25H35BrO8 (M þ H)þ m=z:
543.1594; found: (M þ H)þ m=z: 543.1617.
12-Bromododecyl 4-Acetoxybenzoate (3B). Yellow oil, yield 1.08 g (63%),
limiting reagent: 12-bromododecanol 4.0 mmol; IR: 2926, 2854, 1762, 1720, 1604,

NOVEL PHENOLIC SURFACTANTS
1073
1
1504, 1465, 1413, 1368, 1274, 1196, 1160, 1115, 1100, 913, 763, 702 cmꢁ1. H NMR
(CDCl3, 500 MHz): d ppm 8.00 (d, 2 H, J ¼ 8.5 Hz, ArH), 7.10 (d, 2 H, J ¼ 8.5 Hz,
ArH), 4.24 (t, 2 H, J ¼ 7.0 Hz, CO2CH2), 3.30 (t, 2 H, J ¼ 7.0 Hz, Br-CH2), 2.25
(s, 3 H, OAc), 1.78 (q, 2 H, J ¼ 7.0 Hz, CH2), 1.68 (q, 2 H, J ¼ 7.0 Hz, CH2), 1.30
(m, 16 H, CH2); 13C NMR (CDCl3, 125 MHz): d ppm 168.8, 165.8, 154.1, 131.1,
128.1, 121.5, 65.7, 34.0, 32.8, 29.4, 29.2, 28.7, 26.0, 25.8, 21.1; ESI MS: calcd.
C21H31BrO4 (M þ H)þ m=z: 427.1484; found: (M þ H)þ m=z: 427.1476
General Procedure for the Synthesis of Compounds 4A–4B
The following procedure was an adaptation from Zheng et al.[24] A solution of
potassium thioacetate (1.2 equiv) in dimethylformamide (DMF) (1 mL) was added
to compound 3 (1 equiv) in DMF (0.1 M) at ꢁ78 ꢀC, and the reaction mixture was
warmed to 23 ꢀC and stirred for 48 h. Ethyl acetate was used to transfer the contents
to a separatory funnel. The resulting mixture was then washed with water (5 ꢂ 10 mL).
The organic layer was then washed with Na2CO3(sat) (5 ꢂ 10 mL). The combined aque-
ous layers were extracted with ethyl acetate (2 ꢂ 20 mL). The combined organic layers
were dried with Na2SO4 and filtered through cotton. The resulting mixture was con-
centrated under reduced pressure. The crude product was purified by silica-gel column
chromatography, eluting with mixtures of hexane and ethyl acetate.
5-((12-(Acetylthio)dodecyloxy)carbonyl)benzene-1,2,3-triyl triacetate
(4A). White solid, yield 1.55 g (78%), limiting reagent: 5-((12-bromododecyloxy)
carbonyl)benzene-1,2,3-triyl triacetate (3A) 3.68 mmol; mp (52–53 ꢀC); IR: 2921,
2849, 1773, 1719, 1695, 1471, 1404, 1428, 1374, 1248, 1215, 1191, 1059, 1017, 902,
1
848, 783, 764, 430 cmꢁ1. H NMR (CDCl3, 500 MHz) d ppm 7.71 (s, 2 H, ArH),
4.21 (t, 2 H, J ¼ 7.0 Hz, CO2CH2), 2.79 (t, 2 H, J ¼ 7.5 Hz, COS-CH2), 2.23 (s, 3
H, SAc), 2.24 (s, 9 H, OAc), 1.66 (q, 2 H, J ¼ 7.5 Hz, CH2), 1.48 (q, 2 H, J ¼ 7.5 Hz,
Hz, CH2), 1.19 (m, 16 H, CH2); 13C NMR (CDCl3, 125 MHz): d ppm 196.0, 167.6,
166.4, 164.4, 143.3, 138.5, 128.7, 122.1, 65.7, 30.6, 29.5, 29.4 (3C), 29.2, 29.15, 29.10,
28.8, 25.9, 20.5, 20.1; ESI MS: calcd. C27H38O9S (M þ H)þ m=z: 539.2315; found:
(M þ H)þ m=z: 539.2320.
12-(Acetylthio)dodecyl 4-acetoxybenzoate (4B). White solid, yield 0.68 g
(69%), limiting reagent: 12-bromododecyl 4-acetoxybenzoate (3B) 2.81 mmol; mp
(46–47 ꢀC); IR: 2922, 2853, 1759, 1722, 1607, 1510, 1468, 1410, 1365, 1270, 1191,
1
1123, 1109, 1105, 1113, 919, 756, 710, 600, 550 cmꢁ1. H NMR (CDCl3, 500 MHz):
d ppm 8.06 (d, 2 H, J ¼ 9.0 Hz, ArH), 7.15 (d, 2 H, J ¼ 9.0 Hz, ArH), 4.29 (t, 2 H,
J ¼ 7.0 Hz, CO2CH2), 2.84 (t, 2 H, J ¼ 7.0 Hz, COS-CH2), 2.30 (s, 6 H, SAc), 1.72
(q, 2 H, J ¼ 7.0 Hz, CH2), 1.53 (q, 2 H, J ¼ 7.5 Hz, CH2), 1.35 (m, 16 H, CH2); 13C
NMR (CDCl3, 125 MHz): d ppm 195.9, 168.7, 165.7, 154.1, 131.0, 128.0, 121.5,
65.2, 30.6, 29.4, 29.1, 29.2, 28.7, 25.9, 21.1; ESI MS: calcd. C23H34O5S (M þ H)þ
m=z: 423.2205; found: (M þ H)þ m=z: 423.2205.
General Procedure for the Synthesis of Compounds 1A–1B
The following procedure was a modified procedure of that previously reported
by Wallace and Springer.[25] Sodium thiomethoxide (1 equiv) in MeOH (1 M) was

1074
A. RAJASINGAM ET AL.
added to a stirred solution of 4 (1.11 equiv) in MeOH (0.1 M) at ꢁ78 ꢀC, and the
reaction mixture was warmed to 23 ꢀC and stirred for 48 h. Ethyl acetate was used
to transfer the contents to a separatory funnel. The resulting mixture was then
washed with water (5 ꢂ 10 mL). The organic layer was then washed with Na2CO3(sat)
(5 ꢂ 10 mL). The combined aqueous layers were extracted with ethyl acetate
(2 ꢂ 20 mL). The combined organic layers were dried with Na2SO4 and filtered
through cotton. The resulting mixture was concentrated under reduced pressure.
The crude product was purified by silica-gel column chromatography, eluting with
mixtures of hexane and ethyl acetate.
12,12’-Disulfanediylbis(dodecane-12,1-diyl) bis(3,4,5-trihydroxybenzo-
ate) (1A). White solid, yield 0.33 g (53%), limiting reagent: Sodium thiomethoxide
(1.67 mmol); mp (87–88 ꢀC); IR: 2916, 2848, 2316, 2337, 1716, 1456, 1036, 667,
1
413, 402 cmꢁ1. H NMR (DMSO-d6, 500 MHz) d ppm 9.22 (s, 2 H, ArOH), 8.90
(s, 1 H, ArOH), 6.93 (s, 2 H, ArH), 4.13 (t, 2 H, J ¼ 6.5 Hz, CO2CH2), 1.75 (t, 2
H, J ¼ 6.5 Hz, COS-CH2), 1.59 (m, 2 H, J ¼ 6.5 Hz, CH2), 1.27 (m, 16 H, CH2);
13C NMR (DMSO-d6, 125 MHz) d ppm 166.2, 145.9, 138.7, 120.0, 108.9, 64.3,
39.9, 39.8, 39.6, 39.4, 38.4, 29.4, 29.0, 28.7, 28.1, 25.9. ESI MS: calcd.
C38H58O10S2 (M þ H)þ m=z: 738.3471; found: (M þ H)þ m=z: 738.3473
12-Mercaptododecyl 4-hydroxybenzoate (1B). White solid, yield 0.13 g
(36%), limiting reagent: Sodium thiomethoxide (1.065 mmol); mp (64–65 ꢀC); IR:
1
2922, 2851, 1686, 1608, 1467, 1279, 1056, 772, 418, 410 cmꢁ1. H NMR (CDCl3,
500 MHz) d ppm 7.94 (d, 2 H, J ¼ 9.0 Hz, ArH), 6.87 (d, 2 H, J ¼ 9.0 Hz, ArH),
6.12 (s, 1 H, ArH), 4.28 (t, 2 H, J ¼ 6.5 Hz, CO2CH2), 2.67 (t, 2 H, J ¼ 6.5 Hz,
COS-CH2), 1.74 (q, 2 H, J ¼ 7.5, CH2), 1.64 (q, 2 H, J ¼ 7.0 Hz, CH2), 1.36 (m, 17
H, CH2); 13C NMR (CDCl3, 125 MHz) d ppm 166.8, 160.0, 131.8, 122.8, 115.2,
65.0, 39.2, 29.6, 29.4, 29.2, 28.7, 28.4, 26.0; ESI MS: calcd. C19H30O3S (M þ H)þ
m=z: 339.1994; found: (M þ H)þ m=z: 339.2003.
FUNDING
The authors thank the funding agencies NSERC and FQRNT for their
financial support. C. DeWolf acknowledges the support of the FQRNT Centre for
Self-Assembled Chemical Structures (CSACS).
SUPPORTING INFORMATION
1
Full experimental detail and H and 13C NMR spectra can be found in the
‘‘Supplementary Content’’ section of this article’s Web page.
REFERENCES
1. Laibinis, P. E.; Whitesides, G. M. J. Am. Chem. Soc. 1992, 114, 9022.
2. Prime, K. L.; Whitesides, G. M. Science 1991, 252 (5009), 1164.
3. Lee, M.; Kim, K. H.; Park, J.-G.; Lee, J.-H.; Lim, H.-W.; Park, M.-Y.; Chang, S.-I.; Lee,
E. K.; Lim, D. W.; Choo, J. BioChip J. 2012, 6, 10.
4. Haslam, E. J. Nat. Prod. 1996, 59, 205.

NOVEL PHENOLIC SURFACTANTS
1075
5. Priya, S. S.; Bharani, G.; Nagalingam, M.; Jayanthi, M.; Kanagavalli, U. J. Pharm. Res.
2011, 4, 2228.
6. Favre, M.; Landolt, D. Corros. Sci. 1993, 34, 1481.
7. Oh, H. I.; Hoff, J. E.; Armstrong, G. S.; Haff, L. A. J. Agric. Food Chem. 1980, 28, 394.
8. Crozier, A.; Jaganath, I. B.; Clifford, M. N. Nat. Prod. Rep. 2009, 26, 1001.
9. Santos-Buelga, C.; Scalbert, A. J. Sci. Food Agric. 2000, 80, 1094.
10. Seeram, N. P.; Adams, L. S.; Zhang, Y.; Lee, R.; Sand, D.; Scheuller, H. S.; Heber, D.
J. Agric. Food Chem. 2006, 54, 9329.
11. Aviram, M.; Dornfeld, L. Atherosclerosis 2001, 158, 195.
12. Biebuyck, H. A.; Bain, C. D.; Whitesides, G. M. Langmuir 1994, 10, 1825.
13. Ulman, A. Chem. Rev. 1996, 96, 1533.
14. Schmidt, R.; Carrigan, J. G.; DeWolf, C. E. Can. J. Chem. 2006, 84, 1411.
15. Kubo, I.; Chen, Q.-X.; Nihei, K.-I. Food Chem. 2003, 81, 241.
16. Ximenes, V. F.; Lopes, M. G.; Petronio, M. S.; Regasini, L. O.; Siqueira Silva, D. H.; da
Fonseca, L. M. J. Agric. Food Chem. 2010, 58, 5355.
17. Masuoka, N.; Nihei, K.-I.; Kubo, I. Mol. Nutr. Food Res. 2006, 50, 725.
18. Dodo, K.; Minato, T.; Noguchi-Yachide, T.; Suganuma, M.; Hashimoto, Y. Bioorg. Med.
Chem. 2008, 16, 7975.
19. Wang, G.; Li, L.; Xie, C.; Yu, S.; Liu, F.; Ye, X. Synth. Commun. 2011, 41, 945.
20. Ye, J.; Abiman, P.; Crossley, A.; Jones, J. H.; Wildgoose, G. G.; Compton, R. G.
Langmuir 2010, 26, 1776.
21. Jung, D.-I.; Song, J.-H.; Shin, E.-H.; Kim, Y.-Y.; Lee, D.-H.; Choi, S.-K.; Hahn, J.-T.
Bull. Korean Chem. Soc. 2010, 31, 1031.
22. Lukkari, J.; Meretoja, M.; Kartio, I.; Laajalehto, K.; Rajama¨ki, M.; Lindstro¨m, M.;
Kankare, J. Langmuir 1999, 15, 3529.
23. Gimenez-Lopez, M. D. C.; Ra¨isa¨nen, M. T.; Chamberlain, T. W.; Weber, U.; Lebedeva,
M.; Rance, G. A.; Briggs, G. A. D.; Pettifor, D.; Burlakov, V.; Buck, M.; Khlobystov, A.
N. Langmuir 2011, 27, 10977.
24. Zheng, T.-C.; Burkart, M.; Richardson, D. E. Tetrahedron Lett. 1999, 40, 603.
25. Wallace, O. B.; Springer, D. M. Tetrahedron Lett. 1998, 39, 2693.
26. Holmes, B. T.; Snow, A. W. Tetrahedron 2005, 61, 12339.
27. Gazit, A.; Yaish, P.; Gilon, C.; Levitzki, A. J. Med. Chem. 1989, 32, 2344.
28. Yazaki, R.; Kumagai, N.; Shibasaki, M. Chem. Asian J. 2011, 6, 1778.
29. Hoshino, O.; Yamanashi, Y.; Umezawa, B. Tetrahedron Lett. 1969, 12, 937.
30. Abdel-Aziz, M.; Gamal-Eldeen, A. M. Pharm. Biol. 2009, 47, 854.
31. Kraus, M.; Biskup, E.; Richling, E.; Schreier, P. J. Labelled Compd. Radiopharm. 2006,
49, 1151.