Synthesis and surface properties of alkyl β?D?thioglucopyranoside

Article abstract of DOI:10.1016/j.molliq.2018.11.134

Alkyl thioglycosides are a class of nonionic sugar-based sulfur-containing surfactants and bioreagents. The surfactants 1,2?trans alkyl β?D?thioglucopyranosides with different alkyl chain length (n = 6–12) were stereoselectively prepared by the Helferich method. Their properties including HLB number, logP value, water solubility, foam property, emulsifying property, surface property and thermotropic liquid crystal property were mainly investigated. The results showed that their HLB numbers and water-solubility decreased as the related logP values increased with increasing the alkyl chain length. Alkyl β?D?thioglucosides were already insoluble in water with n ≥ 10. Both β?D?thioglucopyranosides (n = 8, 9) reduced the surface tension of the related aqueous solution to nearly 29 mN·m^?1 at the critical micelle concentration (CMC), they also had excellent foaming ability and foam stability. Nonyl β?D?thioglucopyranoside had good emulsifying properties for both n?octane/water system and toluene/water system. Alkyl β?D?thioglucopyranosides (n = 6–12) were observed to have the thermotropic liquid crystal properties.

Full text of DOI:10.1016/j.molliq.2018.11.134

Accepted Manuscript
Synthesis and surface properties of alkyl β'd'thioglucopyranoside
Xiubing Wu, Langqiu Chen, Fang Fu, Yulin Fan, Zhiqiang Luo
PII:
S0167-7322(18)34458-1
DOI:
Reference:
https://doi.org/10.1016/j.molliq.2018.11.134
MOLLIQ 10044
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
29 August 2018
16 November 2018
26 November 2018
Please cite this article as: Xiubing Wu, Langqiu Chen, Fang Fu, Yulin Fan, Zhiqiang
Luo , Synthesis and surface properties of alkyl β'd'thioglucopyranoside. Molliq (2018),
https://doi.org/10.1016/j.molliq.2018.11.134
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ACCEPTED MANUSCRIPT
Synthesis and Surface Properties of Alkyl β-D-thioglucopyranoside
Authorships and Affiliations
1. Xiubing Wu, e-mail address: 2529721652@qq.com; College of Chemistry,
Xiangtan University, Xiangtan City, 411105, Hunan Province, People’s Republic of
China
2. Langqiu Chen*, e-mail address: chengood2003@263.net; College of Chemistry,
Xiangtan University, Xiangtan City, 411105, Hunan Province, People’s Republic of
China; Telephone: 0086-731-58292449; Fax: 0086-731-58292449; Cell Phone:
0086-13467935586
3. Fang Fu, e-mail address: 1608923099@qq.com; College of Chemistry, Xiangtan
University, Xiangtan City, 411105, Hunan Province, People’s Republic of China
4. Yulin Fan, e-mail address: 965774223@qq.com; College of Chemistry, Xiangtan
University, Xiangtan City, 411105, Hunan Province, People’s Republic of China
5. Zhiqiang Luo, e-mail address: 1693623064@qq.com; College of Chemistry,
Xiangtan University, Xiangtan City, 411105, Hunan Province, People’s Republic of
China.

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Synthesis and Surface Properties of Alkyl
β-D-thioglucopyranoside
Xiubing Wu, Langqiu Chen*, Yunlin Fan, Fang Fu, Zhiqiang Luo
College of Chemistry, Key Laboratory of Environmentally Friendly Chemistry and Application of
Ministry of Education, Xiangtan University, Xiangtan, 411105, Hunan, People’s Republic of China
Abstract
Alkyl thioglycosides are a class of nonionic sugar-based sulfur-containing
surfactants and bioreagents. The surfactants 1,2-trans alkyl β-D-thioglucopyranosides
with different alkyl chain length (n = 6–12) were stereoselectively prepared by the
Helferich method. Their properties including HLB number, logP value, water
solubility, foam property, emulsifying property, surface property and thermotropic
liquid crystal property were mainly investigated. The results showed that their HLB
numbers and water-solubility decreased as the related logP values increased with
increasing the alkyl chain length. Alkyl β-D-thioglucosides were already insoluble in
water with n ≥ 10. Both β-D-thioglucopyranosides (n = 8, 9) reduced the surface
tension of the related aqueous solution to nearly 29 mN·m-1 at the critical micelle
concentration (CMC), they also had excellent foaming ability and foam stability.
Nonyl β-D-thioglucopyranoside had good emulsifying properties for both
n-octane/water system and toluene/water system. Alkyl β-D-thioglucopyranosides (n =
6–12) were observed to have the thermotropic liquid crystal properties.
Keywords: Alkyl β-D-thioglucopyranoside; Water solubility; Sugar-based surfactants;
Surface activity; Thermotropic liquid crystalline
* E-mail：chengood2003@263.net

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1. Introduction
It is well-known that the glycosylic bonds can be classified as O-glycosylic bond
[1], S-glycosylic bond [2], Se-glycosylic bond [3], N-glycosylic bond [4],
C-glycosylic bond [5]. Indeed, the uncountable glycosides were found in nature [3, 6].
Alkyl (poly)glycosides (APGs) are a very interesting kind of multifunctional
nonionic polyhydroxy surfactants, which contain a hydrophilic glycosyl head (such as
glucosyl, maltosyl and xylosyl group) and a hydrophobic alkyl tail (saturated or
unsaturated chain ) [7–9]. As a kind of well-known industrial products, APGs and
their anomerically pure 1,2-cis or 1,2-trans alkyl glycosides all have bestowed
excellent surface activity, foaming, emulsifying properties, biodegradability,
little-to-no toxicity and antibacterial properties [7, 10–13], and thereof they are used
in a broad range of scientific research, industrial and consumer applications, such as
membrane protein [14], textile industry [15], agrochemicals [16], functional materials
[17], detergent, emulsifier, food, cosmetics and so on[18]. In addition, some alkyl
glycosides can form a micellar so that they would be expected to encapsulate drug
molecules to exercise drug carriers in the pharmaceutical industry [19, 20].
Compared with well-known alkyl (poly)glycosides and the related anomerically
pure glycosides [21–23], there are not so many researches on preparation, properties
and the related application of alkyl thioglycosides [2, 24, 25]. As a class of
sugar-based nonionic sulfur-containing surfactants, alkyl thioglycosides are also
amphipathic, biodegradable, low-to-no hydrolase activity and low toxicity, which

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should be practically used in detergents and other fields [25].
In the field of life science, alkyl thioglycoside can be used as a the effective
medium to extract the membrane protein to stabilize further the structure and function
of the extracted protein. For instance, although octyl β-thioglucoside (OTG) (4c) has
an anomical structure and a critical micelle concentration (CMC) similar to octyl
β-glucoside (OG) (OTG: CMC, 9 mM; OG: CMC, 23–25 mM [26]), OTG was
considered as a highly efficient and mild nonionic detergent superior to OG because
the OTG-solubilized membrane protein bacteriorhodopsin (BR) was high structural
stability with the specific BR trimeric complexes in the dark and under light
illumination since the apparent activation energy of denaturation of the
OTG-solulized BR was calculated approximately twice as high as that of denaturation
of the OG-solulized BR, and the subsequent removal of OTG was readily performed
by dialysis in the reconstitution process into the related lipid bilayer membrane since
OTG had enough high CMC value (9.0 x 10-3 mol·L-1) [27, 28].
As is known to all, the hydrophile-lipophilic balance (HLB) number and the
water solubility of alkyl glycosides would be gradually reduced with increasing the
alkyl chain length [29]. However, with the higher HLB number and bigger
water-solubility, the related surfactants were found to arrange difficultly in the
air-solvent interface so that it would be easy to cause their poor surface activities and
low practical applicable value as surfactants/detergents. As the other side of a coin,
the longer alkyl chain would cause the lower HLB number and poor water-solubility,
such surfactants/detergents would be not easy to construct spontaneously the

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oil-in-water (O/W) micellar microstructure by supramolecular self-assembly,
therefore their practical application would be obviously restricted to some extent as
well [30, 31]. In general, a glycoside should be used as a good stabilizer for O/W
emulsions as HLB = 8–15; on the opposite, and it should be applied to stabilize
water-in-oil (W/O) emulsions as HLB = 3–6. In the comparison, it should be used as
detergent as well.
Since alkyl thioglycosides haven’t been well studied for their preparation [25,
32], surface activity [33], phase behavior [34], thermotropic liquid crystal property
[35], therefore their research should be explored further to disclose their
struture-property relationships convenient for their application in science, life and
functional materials.
In the paper, we planned to prepare a series of 1,2-trans alkyl
β-D-thioglucopyranosides (also called as alkyl β-D-1-thioglucopyranosides, alkyl
1-thio-β-D-glucopyranosides [36], 1-S-alkyl β-D-thioglucopyranosides [37] or
alkylthio β-D-glucopyranosides [38]) with different alkyl chain length (Scheme 1) by
the glycochemistry method [36], and investigate their physicochemical properties
involving in HLB number, logP value, water solubility, surface activity and
thermotropic liquid crystal property to further disclose their structure-properties
relationships. The investigation should provide valuable theoretical parameters for
scientific research and applicable prospects as nonionic sugar-based sulfur-containing
surfactants/detergents.

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2. Experimental
2.1 Materials and instruments
All detailed chemical reagents and the instruments used for the preparation and
characterization of the target thioglycosides were presented in the Elemenary
Supporting Information (ESI).
The corresponding chemical structures were confirmed by 1H NMR
spectroscopy which was recorded by Bruker Avance 400 spectrometers when the
products were dissolved in CDCl3, D2O or DMSO-d6. Surface tension was obtained
with a DP-A precision digital manometer. Differential scanning calorimetry (DSC,
TA-Q10, TA Instruments) was used for tracking the thermal transitions of the samples
through a heating and cooling procedure at a scanning rate of 10 oC/min with nitrogen
as sweeping fluid. Benzoic acid and indium were used as the standard sample to
calibrate the heat flow and temperature. The samples with 3 ~ 5 mg were encapsulated
in the sealed aluminum pans. The liquid crystal textures of the samples were carried
out by a polarized optical microscopy (POM, Leica DM-LM-P) equipped with a Leica
heating stage (FP82HT) under the different temperatures. The samples were heated
and cooled at 5 oC/min.
2.2 Synthesis
Alkyl β-D-thioglucopyranosides (4a ~ 4f, n = 6, 7, 8, 9, 10, 12) (Scheme 1) were
synthesized with D-glucose and mercaptans (n = 6, 7, 8, 9, 10, 12) as the raw
materials by the literature method [36]. The detailed synthetic processes can be
available in the ESI.

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2.3 General methods
2.3.1. Hydrophile-lipophilic balance (HLB) and octanol-water coefficient (logP)
The HLB numbers of the prepared alkyl β-D-thoglucopyranosides were
calculated from Eq. (1) by the Griffin method [1, 10].
20퐻
HLB=
(1)
퐻+푂
In the equation, H and O represented the quality of hydrophilic sugar part
(including sulfur atom) and lipophilic alkyl chains, respectively.
The octanol-water partition coefficient (logP) values of alkyl
β-D-thioglucopyranosides were calculated by ChemBioDraw (Ultra 14.0) to estimate
their hydrophobicity and hydrophilicity [1, 29].
2.3.2 Solubility
The solubility of alkyl β-D-thioglucopyranosides in water or ethanol was
determined at room temperature (25 °C) with the described methods [10, 39].
2.3.3 Surface tension
The surface tension of alkyl β-D-thioglucopyranosides was determined by
maximum bubble pressure method (MBPM) [10, 40–42]. First, a series of different
concentrations of aqueous solution of alkyl β-D-thioglucopyranosides (4a ~ 4d) were
prepared to record the related maximum additional stress (Δp) respectively. With
distilled water as a reference, the constant K was readily calculated according to the
Laplace formula (Eq. (2)) and surface tension (γ) of the water at 25 °C. The surface
tension of a series of different concentrations were next calculated out respectively.
The obtained data were drawn to show the relationship between the surface tension

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and the concentration. The slope (dγ/dlnC) was obtained by fitting the curves of
surface tension and concentration below CMC. According to Eq. (3), the surface
excess concentration of monolayer saturated adsorption (Γmax) was calculated out. The
average molecular cross-sectional area (Amin) was calculated by Eq. (4) [8]. Herein, R
= 8.314 J∙mol-1∙K-1 and n = 1 since such thioglucopyranoside is classified as a
nonionic surfactant; T is the thermodynamic temperature (K).
γ=K∆p
(2)
(3)
1
푑훾
훤
= − 푅푇 · (푑ln퐶)
max
푝
1
퐴min
=
(4)
푁 훤
퐴 max
The effectiveness of reducing surface tension (πCMC) was obtained by Eq. (5).
The efficiency of reducing surface tension (pC20) was calculated by Eq. (6) [8].
πCMC =γ0-γCMC
pC20 = -lgC20
(5)
(6)
Herein, γ0 represented the surface tension of the distilled water, γCMC was the
surface tension of aqueous solution at the CMC, C20 was the concentration of the
aqueous surfactant solution while the surface tension was reduced by 20 mN·m-1 in
the aqueous solution.
The standard micellization free energy (ΔGmic) and surface adsorption free
energy (ΔGads) of alkyl β-D-thioglucopyranosides in aqueous solution were also
calculated out by Eq. (7) and (8) respectively [42, 43].
(
)
∆퐺mic = 푅푇ln 퐶CMC
(7)
(8)
휋
CMC
∆퐺ads = ∆퐺푚푖푐
−
훤
max

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2.3.4 Foaming property
According to the literature[42], the foaming property of the aqueous solution of
alkyl β-D-thioglucopyranosides was determined at 25 °C. An aqueous solution of
alkyl β-D-thioglucopyranosides with mass fraction of 0.25% and volume of 10 mL
was obtained and placed in 100-mL graduated cylinder with a plug. The initial volume
of foam (V0) was recorded just after 60 seconds of intense shock, and the foaming
performance was evaluated according to the initial volume of foam. Just after the
solution kept in static state for 5 min, the foam volume (V5) was recorded, the foam
stability was evaluated according to the foam disappearance rate (υ) which was
calculated by Eq. (9).
푉 −푉
0
5
휐 =
(푐푚3/푠)
푡
(9)
2.3.5 Emulsifying property
An aqueous solution of alkyl β-D-thioglucopyranosides with mass fraction of
0.25% was prepared. A 20 mL aqueous solution of alkyl β-D-thioglucopyranosides
was put into 100-mL cylinder with a plug, then 20 mL of n-octane or toluene as the oil
phase was added, the mixture was strongly shocked for 60 sec. After the solution kept
in static state for 1 h, the volumes of the water layer, the emulsion layer and the oil
layer were recorded respectively. The emulsifying strength was determined according
to the volume of the emulsion layer [42].
2.3.6 Thermotropic phase behavior

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The thermal phase transition behavior of alkyl β-D-thioglucopyranoside was
observed by polarizing microscopy (POM) during the heating and cooling process,
o
and rate of temperature changed was controlled at 5 C∙min-1. The phase transition
temperature of alkyl β-D-thioglucopyranosides was measured by differential scanning
calorimeter (DSC) [1, 29].
3. Results and discussion
3.1 Synthesis and characterization of alkyl β-D-thioglucopyranoside
HO
HO
HO
AcO
AcO
AcO
AcO
AcO
AcO
O
Ac2O
O
O
RSH
OAc
SR
OH
BF3•Et2O
NaOAc
OH
OAc
OAc
1
2
3
HO
HO
HO
R = n-C6H13, n-C7H15, n-C8H17
MeONa
MeOH
O
a
b
c
SR
n-C9H19, n-C10H21, n-C12H25
OH
d
e
f
4
Scheme 1. Synthesis of alkyl β-D-thioglucopyranoside
In fact, alkyl β-D-thioglucopyranosides (4a ~ 4f) were prepared by a lot of
glycochemistry method. Saito [24] prepared some β-D-thioglucopyranosides by
thiourea method. Glycosyl bromide was reacted with thiourea and subsequent reaction
with alkylbromide and the final deacetylation was taken to obtain the related
thioglycoside. The procedure was rather complex and glycosyl bromide wasn’t stable
in spite of proper yield without using any expensive reagent. Li’s group [24] reported
better thioglycosylation of 1,2-cis-glycosyl acetates to obtain the related compounds

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aryl β-thioglycosides with boron trifluoride diethyl etherate (BF3·Et2O) as Lewis acid
catalyst rather than other Lewis acid catalysts. Gurudutt’s group also reported
thioglycosylation using glcosyl halides and zinc salts of thiol in reflux to obtain the
mixture of proportional variable α/β anomers since the direct condensation of
peracetylsugar with mercaptans was not smooth/effective and led to unexpected
results because the initially formed alkyl β-thioglycosides anomerized under the
influence of the catalyst (zinc chloride, tin (IV) chloride, boron trifluoride or
p-toluene sulfonic acid) to give a 7:3 α/β mixture [37]. They also found that the
S-glycosidation of Me3CSH and AllSH was much strange and failed to yield the
corresponding glucosides, probably due to their inability to form the ion-quadruplet
intermediate. Doren’s group [36] investigated that the direct condensation of
peracetylated monosaccharides and the appropriate n-alkylanethiol by the BF3·Et2O
method had the advantage over a Königs-Knorr type of route.
In the paper, the homologous series of kinetically controlled alkyl
β-D-thioglucopyranosides (n = 6, 7, 8, 9, 10, 12) were prepared by the direct
glycosylation method [36], and the method should be reasonable since the acetoxy
group on C-2 would provide anchimeric assistance for the loss of the acetoxy group at
the anomeric centre and lead to form an acyloxonium ion intermediate, and then such
cyclic intermediate was most easily attacked by the thiol on the β-side to obtain 1,2-
trans protected alkyl thioglycoside. As described in Scheme 1, D-glucose (1) was
acetylated to afford 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose (2), the latter was
condensated with mercaptan (n = 6, 7, 8, 9, 10, 12) with boron trifluoride diethyl

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etherate
(BF3·Et2O)
as
Lewis
acid
catalyst
to
provide
alkyl
2,3,4,6-tetra-O-acetyl-β-D-thioglucopyranoside (3). The protected thioglycoside (3)
was deacetylated to obtain the target poduct alkyl β-D-thioglucopyranoside (4).
The condensation reaction should produce a mixture (β (main) and α (less)) of
two anomers whose configuration differs completely from each other at C1 position.
Since the column separation was introduced to make a successful attempt to obtain
anomerically pure 1,2-trans protected alkyl β-D-thioglucopyranosides (3a ~ 3f). The
1
characterization of the anomeric configuration was further confirmed by H NMR
method. For example, the chemical shift (coupling constant, J1,2) of hexyl
2,3,4,6-tetra-O-acetyl-β-D-thioglucopyranoside (3a) was 4.48 ppm (10.0 Hz). Hexyl
2,3,4,6-tetra-O-acetyl-β-D-thioglucopyranoside (3a) was deacetylated to get alkyl
β-D-thioglucopyranoside (4a) without change of anomeric configuration. Other alkyl
β-D-thioglucopyranosides (4b ~ 4f) also were successfully prepared with the same
glycochemical procedure.
The
1,2-trans
anomeric
configurations
of
alkyl
2,3,4,6-tetra-O-acetyl-β-D-thioglucopyranosides (3a ~ 3f) were readily characterized
1
with H NMR spectral analysis (in the ESI) since their H-1 chemical shifts (coupling
constants J1,2) in CDCl3 all were 4.48 ppm (10.0 Hz, D2O) (3a ~ 3f). Meanwhile, the
1,2-trans anomeric configurations of alkyl β-D-thioglucopyranosides (4a ~ 4f) all
were readily characterized with 1H NMR spectral analysis (in the ESI) since their H-1
chemical shifts (coupling constants J1,2, deuterium solvent) were 4.47 ppm (9.8 Hz,
D2O) (4a), 4.48 ppm (9.9 Hz, D2O) (4b), 4.43 ppm (9.9 Hz, D2O) (4c), 4.20 ppm (9.7

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Hz, DMSO-d6/D2O) (4d), 4.20 ppm (9.7 Hz, DMSO-d6/D2O) (4e), 4.20 ppm (9.7 Hz,
DMSO-d6/D2O) (4f).
Indeed, 1,2-trans O-glucopyranoside generally showed the coupling constant J1,2
= 4–8 Hz, for instance, H-1 chemical shifts (coupling constants J1,2) of alkyl
β-D-glucopyranoside were 4.20–4.51 ppm (J1,2 = 6.3–7.9 Hz)) [44]. However, a lot of
1,2-trans S-glucopyranosides had higher coupling constants J1,2. (n-propyl
2,3,4,6-tetra-O-acetyl-β-D-thioglucopyranoside
2,3,4,6-tetra-O-acetyl-α-D-thioglucopyranoside 5.7 Hz [38], S-Trifluoromethyl
2,3,4,6-tetra-O-benzoyl-1-thio-β-D-glucopyranoside 9.9 Hz [45],
2,3-di-O-Acetyl-1-S-acetyl-4,6-bis-O-(4-bromobenzoyl)-1-thio-β-D-glucopyranose
10.5 Hz [46], cyclohexyl
10.0
Hz
[38],
n-propyl
2,3-di-O-acetyl-4,6-bis-O-(4-bromobenzoyl)-1-thio-β-D-glucopyranoside 10.1 Hz
[46]). Therefore, the results elucidated that the 1,2-trans β-anomer alkyl
β-D-thioglucopyranosides (n = 6, 7, 8, 9, 10, 12) were successfully formed.
3.2 HLB number, logP and solubility
The HLB number of alkyl β-D-thioglucopyranosides (n = 6–12) (4a ~ 4f) was
calculated by the Griffin method on condition that the hydrophilic part contained
sulfur atom, and the results were listed in Table 1. From Table 1, the HLB number
(13.9 → 10.7) of alkyl β-D-thioglucopyranoside (n = 6 → 12) was bigger than the
HLB number (13.6 → 10.3) of alkyl β-D-glucopyranoside (n = 6 → 12) with the same
alkyl chain length.

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On the opposite, the logP value (0.78 → 3.29) of alkyl β-D-thioglucopyranoside
(n = 6 → 12) was bigger than the logP value (0.06 → 2.57) of alkyl
β-D-glucopyranoside (n = 6 → 12) with the same alkyl chain length from Table 1.
The data should be considered as right and rather valuable since the hydrophilicity of
sulfur atom is weaker than that of oxygen atom, i.e. the lipophilicity of sulfur atom is
stronger than that of oxygen atom. Since logP > 0, alkyl β-D-thioglucopyranoside (n =
6, 7, 8, 9, 10, 12) had different degrees of lipophilicity although there was somewhat
hydrophilicity due to its hydrophilic glucopyranosyl head [1]. In addition, the longer
the alkyl group and the stronger the lipophilicity.
Table
1
HLB number and logP value of alkyl β-D-glucopyranoside [44] and
β-D-thioglucopyranoside
Alkyl β-D-gluco-
logP
HLB
number
13.6
Water
solubility
high
Alkyl β-D-thiogluco-
logP
HLB
number
13.9
New HLB
number
11.7
Water
solubility
high
pyranoside (n)
pyranoside (n)
6
7
0.06
0.48
0.90
1.31
1.73
2.57
6
7
0.78
1.20
1.62
2.04
2.45
3.29
12.9
high
13.3
11.2
high
8
12.3
soluble
soluble
low
8
12.7
10.6
soluble
low
9
11.7
9
12.1
10.2
10
12
11.2
10
12
11.6
9.8
insoluble
insoluble
10.3
insoluble
10.7
9.0

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Fig. 1 Solubility of alkyl β-D-thioglucopyranoside in water or ethanol
The results of the solubility of alkyl β-D-thioglucopyranosides (4a ~ 4f) were
shown in Fig. 1. Their solubility in water and ethanol decreased gradually with
increasing the alkyl chain length. At the beginning, the solubility of hexyl
β-D-thioglucopyranoside (4a) in water is slightly higher than that in ethanol. The
solubility (44.1 g) of nonyl β-D-thioglucopyranoside (4d) in ethanol is obviously
higher than that in water (4.3 g). While n ≥ 10, the related β-D-thioglucopyranosides
(4e ~ 4f) are soluble in ethanol and insoluble in water.
Whilst inspecting again the calculated HLB number in Table 1 by Eq. (1), such
data should be naturally considered as really accessible/convenient but rather strange
since the electronegativity of sulfur atom is 2.58, which is obviously less than the
strong electronegativity of oxygen atom (3.44), almost equivalent to the
electronegativity of carbon atom (2.55), i.e. the sulfur atom was considered to have
stronger lipophilicity and weaker hydrophilicity. Therefore, a new idea/whim was
introduced to recalculate HLB number (called as a new HLB numbr) by Eq. (10) from
the Griffin method on condition that the hydrophilic part only involved partially sulfur
atom.
HLB= 20(푆+1.08)
(10)
푇
In the new HLB equation, S represented the quality of hydrophilic sugar part
(without sulfur atom), and T represented total molecular quality. The value 1.08 was a
calculated result from 0.03*32.07/0.89 since the difference between electronegativity

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of oxygen atom (3.44) and electronegativity of carbon atom (2.55) was 0.89 and the
difference between electronegativity of sulfur atom (2.58) and electronegativity of
carbon atom (2.55) was 0.03, and as well 32.07 was mass of sulfur atom.
The calculated data (the new HLB numbers) were also listed in Table 1. It was
interesting that the new equation was effectively supported according to the
experimental data although the equation was somewhat curious. The new HLB
number (11.7 → 9.0) of alkyl β-D-thioglucopyranoside (n = 6 → 12) was smaller than
the HLB number (13.6 → 10.3) of alkyl β-D-glucopyranoside (n = 6 → 12) with the
same alkyl chain length. Meanwhile, the related thioglucopyranoside (n = 6–9) had
water solubility on condition that the new HLB number > 10, for instance, nonyl
thioglucopyranoside (4d) still had small water solubility; and the new HLB number <
10, the related thioglucopyranosides (n = 10 (4e), 12 (4f)) did not have water
solubility.
3.3 Interfacial Property
The maximum bubble pressure method (MBPM) was used to measure the
surface tension of different concentration of aqueous alkyl β-D-thioglucopyranosides
(4a ~ 4d) solution at 25 °C. On the opposite, the surface tension of alkyl
β-D-thioglucopyranosides (4e ~ 4f) weren’t investigated because their solubility in
water was too low to be measured.
The relationship curve between the surface tension and the concentration was
shown in Fig. 2, and the resulting data were summarized in Table 2. From Fig. 2 and

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Table 2, alkyl β-D-thioglucopyranosides (4a ~ 4d) were observed to reduce
significantly the surface tension (γ) of their aqueous solutions. The surface tension
value (γCMC) decreased with increasing the alkyl chain length at the CMC, the γCMC
data of octyl β-D-thioglucopyranoside (4c) and nonyl β-D-thioglucopyranoside (4d)
aqueous solutions at their CMC reached the lowest (29.63 mN·m-1). Furthermore, the
CMC value showed a decreasing trend with increasing the alkyl chain length.
In addition, the related molecular cross-sectional area (packing area, Amin) was
found to have a downward trend (42.48 Å2 → 23.82 Å2) with increasing the alkyl
chain length (n = 6 → 9). On the contrary, the surface excess concentration (Γmax
)
tended to increase (3.91x10-6 mol·m-2 → 6.97x10-6 mol·m-2) with increasing the alkyl
chain length (n = 6 → 9). The reason should be that there was a repulsive force
between hydrophobic alkyl chain and water and as well an attractive force between
hydrophilic glycosyl head and water. The increase of the alkyl chain length made it
easier for alkyl β-D-thioglucopyranoside to adsorb on the air/water interface and
further form the related interface layer via the ordered alignment and self-assembling
behavior since more hydrocarbon units should increase the hydrophobicity and
increase the distance with water. Compared with the short alkyl chain in a
homologous series, the long alkyl chain should indeed enhance effectively the
microphase separation of the thioglycosidic molecules and their close alignment each
other involving in several forces such as the hydrophobic-hydrophobic interactions
(Van der Waals forces, dispersion forces, London dispersion forces) of the alkyl chain
and the hydrophilic-hydrophilic interactions (hydrogen bonds) of the glycosyl head at

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the air/water interface. In addition, such sulfur atom with somewhat amphipathicity
perhaps also gave the special contribution to the microphase separation and the
stability of the two dimensional (2D) and/or three dimensional (3D) supermolecular
network structure newly formed since it has higher atomic number, bigger atomic
radius, smaller electronegativity, weaker electron-binding ability, lower ionization
energy and better polarizability/deformability than oxygen atom with high
hydrophilicity (also considered as poor amphipathicity and no lipophilicity). The
experimental results, based just on the multifunctional interactions, showed that they
had monotonic changes for the related CMC, γCMC, Γmax and Amin data in the range of
alkyl chain (n = 6-9), such gradation in their surface phenomenon is really typical of a
homologous series.
Fig. 2 Surface tension of alkyl β-D-thioglucopyranoside (4a ~ 4d)
Table 2 Interfacial property of alkyl β-D-thioglucopyranoside
Thioglycoside (n)
CMC (mol·L-1)
γCMC (mN·m-1)
6
7
8
9
8.21×10-2
2.72×10-2
1.04×10-2
2.80×10-3
32.80
31.75
29.63
29.63
Γmax (10-6 mol·m-2)
3.91
4.21
5.43
6.97

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Αmin (Å2)
42.48
1.88
39.46
2.42
30.59
2.74
23.82
3.15
pC20 (mol·L-1)
πCMC (mN·m-1)
∆Gmic (kJ·mol-1)
∆Gads (kJ·mol-1)
39.17
-6.20
-16.22
40.22
-8.94
-18.49
42.34
-11.33
-19.18
42.34
-14.59
-20.66
In Table 2, the related efficiency (pC20) of reducing the surface tension showed
an increasing trend with increasing the alkyl chain length. The effectiveness (πCMC) of
reducing surface tension first increased rapidly, and then increased slowly to the
maximum with increasing the alkyl chain length. Both πCMC of octyl
β-D-thioglucopyranoside (4c) and nonyl β-D-thioglucopyranoside (4d) solutions
reached the highest (42.34 mN·m-1). Therefore, octyl β-D-thioglucopyranoside (4c)
and nonyl β-D-thioglucopyranoside (4d) had the greatest surface activity. Herein, such
excellent amphiphilic molecules should self-aggregate readily at the air/solution
interface and reduce effectively the corresponding CMC values.
The result of the standard micellization free energy (ΔGmic) and surface
adsorption free energy (ΔGads) was also shown in Table 2. All values were negative,
which indicated that alkyl β-D-thioglucopyranosides (4a ~ 4d) with amphiphilicity
had a tendency to form micelles in the solution, and also possessed an adsorption
capacity at the air/water interface. Both ΔGmic and ΔGads values were observed to
change more negative with increasing the alkyl chain length and such phenomenon
indicated that the longer alkyl chain should have more chance to form micelles in the
solution and migrate to air/solution interface. In addition, ΔGads value was more
negative than ΔGmic value. It was inevitable that all amphiphilic molecules were easy
to adsorb at the air/water interface rather than forming micelles in water when the

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concentration of alkyl β-D-thioglucopyranosides (4a ~ 4d) was below CMC.
3.4 Foaming property and emulsifying property
The foam properties of any surfactants can be readily measured. The bigger the
foaming volume, the better the foaming performance; the slower the rate of foam
disappearing, the better the stability of the foam. In this paper, the volume of foam
and the rate of foam disappearance of a certain concentration of alkyl
β-D-thioglucopyranosides (4a ~ 4d) were measured by the above-described method.
In Fig. 3, the results showed that the initial foam volume (V0) increased first and
then decreased with increasing the alkyl chain length. Hexyl β-D-thioglucopyranoside
(4a) showed the weakest foaming ability (V0 = 20 cm3), and octyl
β-D-thioglucopyranoside (4c) showed the strongest foaming ability (V0 = 88 cm3).
When n ≥ 8, the rate of foam disappearance rapidly decreased, showing good stability.
In general, the foam stability should be determined by the strength of the foaming
performance, and there should be a reasonable illustration that the surfactants would
be adsorbed on the air/solution interface to form a rather sturdy adsorption film to
stabilize the foam.

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Fig. 3 Foam property of alkyl β-D-thioglucopyranoside (4a ~ 4d)
From Fig. 4, the results showed that alkyl β-D-thioglucopyranosides (4a ~ 4d)
had some emulsifying ability for both octane/water and toluene/water immiscible
phase systems, and the emulsification capacity increased with increasing the alkyl
chain length. Nonyl β-D-thioglucopyranoside (4d) had the best emulsifying ability in
both systems. In the process of emulsification, alkyl β-D-thioglucopyranoside with the
longer alkyl chain separated itself more easily away from the bulk solution and was
adsorbed onto the interface to form readily a stronger interfacial film, preventing the
discontinuous liquid particles of disperse phase in the emulsion from reaggregation,
so as to maintain the stability of the emulsion. However, when n ≥ 10 and logP ≥ 2.45,
alkyl β-D-thioglucopyranosides did not have emulsifying property since the related
hydrophilicity was rather weak due to the double function from the hydrophobicity of
alkyl chain and the amphiphilicity of sulfur atom, and the related hydrophobicity was
special strong. In the process of oil/water emulsification, the reasonable alternative
range of the logP value should be carefully considered, such as a choice of 1.50 ≤
logP ≤ 2.04 maybe is laudable or even perfect. The higher logP value would destroy
the dynamic balance partly due to violating the Bancroft rule [47, 48].
In addition, the selected oil phase was different, the emulsified effect was
different each other. Herein, toluene was used as the oil phase, the obtained result was
the emulsion layer and oil layer. In the comparison, n-octane was used as an oil phase,
the obtained result was the emulsion layer and excess water.

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Fig. 4 Emulsifying property of alkyl β-D-thioglucopyranoside
(1) n-octane/water system, (2) toluene/water system
3.5 Thermotropic liquid crystal property
Polarizing optical microscopy (POM) and differential scanning calorimeter (DSC)
were used to study the phase behavior of the related thermotropic liquid crystals.
Table
3
showed that the phase transition temperature of alkyl
β-D-thioglucopyranosides (4a ~ 4f) and the related enthalpy value during the second
heating process obtained by DSC. Fig. 5 showed the DSC patterns for the second
heating of alkyl β-D-thioglucopyranosides (4a ~ 4f). Some thioglucopyranosides (4c ~
4f) showed a double melting phase transition temperatures at heating process: (1) the
liquid crystal temperature (Tlc) from the crystallized solid turned into a translucent
liquid crystal, (2) the liquid crystal disappearing temperature (Tiso) from a translucent
liquid crystal into an isotropic liquid, also called as the clear point temperature.
Table 3 Thermotropic transition temperature of alkyl β-D-glucopyranoside [44] and alkyl
β-D-thioglucopyranoside under the second heating process with DSC scan
∆Hiso
Alkyl β-D-gluco-
Alkyl β-D-thiogluco-

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(kJ·mol-1)
2.7
Tlc(C)
Tiso(C)
∆T(C)
Tlc(C)
－
Tiso(C)
70.2
∆T(C)
－
pyranoside (n)
pyranoside (n)
6
7
90.6
73.2
67.4
73.3
76.6
78.2
-
-
6
7
－
101.9
124.5
139.7
147.1
160.6
－
5.8
80.5
7.3
57.4
61.8
64.8
62.5
67.1
77.9
82.3
98.1
5.2
8
105.4
119.9
127.1
141.6
38.0
46.6
50.5
63.4
8
7.4
9
9
6.1
10
12
10
12
5.7
As shown in Table 3, the melting points of alkyl β-D-thioglucopyranosides (4c ~
4e) increased with increasing the alkyl chain length during heating process, but the
melting point of dodecyl β-D-thioglucopyranoside (4f) turned to decrease since its
hydrogen bonding network would be weaken as glucopyranosyl part became small to
some content in solid crystal state despite that its Van der Waals interactions should
slightly increase [49, 50]. Relatively, the related Tiso still increased monotonously with
increasing the alkyl chain length, and the Tiso vulue of dodecyl
β-D-thioglucopyranoside (4f) reached as high as 160.6 C. The gap (∆T) between
phase transition temperatures also increased with increasing the alkyl chain length.
Besides, there was no obvious relationship between the enthalpy change and the alkyl
chain length each other.
Liu [44] also showed the similar phase transition process of alkyl
β-D-glucopyranosides (Table 3). In the O-glycosides and the S-glycosides due to the
difference between sulfur atom and oxygen atom, there were the same and different
points as follows: (1) both of hexyl β-D-glucopyranoside and hexyl
β-D-thioglucopyranoside (4a) had only one phase transition temperature; (2) heptyl
β-D-thioglucopyranoside (4b) had only one phase transition temperature although

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heptyl β-D-glucopyranoside had two phase transition temperatures; (3) for both of
other β-D-glucopyranosides and β-D-thioglucopyranosides with n = 8, 9, 10, 12), there
were two phase transition temperatures; (4) the S-glycosidic linkage had lower Tlc
value and higher Tiso value than the related O-glycosidic linkage with the same alkyl
chain length, therefore the corresponding difference (∆T) of β-D-thioglucopyranoside
was broader than that of the related β-D-glucopyranoside. Compared with small
atomic radius and strong hydrophilicity of oxygen and fine intermolecular hydrogen
bonding network of the O-glycosides, sulfur atom had amphipathicity to some extent
and made the intermolecular hydrogen bond network of the S-glycosides weaken
although there probably were small improvement/promotion for the intermolecular
interactions between nonopolar alkyl chain and sulfur atom. In addition, sulfur atom
had big atomic radius and perhaps obstructed intermolecular close alignment and high
orientation in the related ordered crystal structure. Such issue would further result in
the reduction of the corresponding Tlc and somewhat enhancement of liquid
crystalline phase temperature range, and the polarizability/deformability of sulfur
atom should also take part in the synergistic action. The homologous S-glycosides
with wide mesomorphic temperature range (∆T) and other characters would probably
have their potential and unexpected values in many cases such as life sciences and
material sciences.

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Fig. 5 DSC curve of alkyl β-D-thioglucopyranoside
Nonyl β-D-thioglucopyranoside (4d) was investigated as shown on the left side
of Fig. 5. At first, the related two endothermic peaks at heating process were
successively observed and considered as melting point peak and clear point
temperature peak. Seconding, an exothermic peak was observed since the isotropic
liquid was transformed into a liquid crystalline phase at cooling process and the
process was exothermic. Thirdly, the second heating process caused another
endothermic peak. And the characteristic peak and the exothermic peak were really
similar each other in appearance and size apart from the opposite direction [1].
POM was used to observe the thermotropic liquid crystalline behavior of alkyl
β-D-thioglucopyranosides (4a ~ 4f) during heating process, so as to disclose the
relationships between their alkyl chain length and thermotropic liquid crystalline
properties, and the results were showed in Fig. 6. Alkyl β-D-thioglucopyranosides (4a
~ 4f) were observed to have birefringence. Their thermotropic liquid crystal texture
was examined during the process of heating under a polarizing microscope. Octyl
β-D-thioglucopyranoside (4c) only appeared a clear Maltese cross pattern texture.

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However, other alkyl β-D-thioglucopyranosides (4a, 4b, 4d, 4e, 4f) appeared vague or
even unformed Maltese cross pattern texture. During cooling, all thioglucopyransides
(4a ~ 4f) showed clear focal-conic fan textures, and such textures of several samples
(4c ~ 4f) were more stylish. These fan structures should be the common
characteristics of the smectic A phase [50, 51]. The focal-conic fan textures still
maintained unchanged even if the temperature was reduced to room temperature. And
the observed thermotropic liquid crystal characteries of such nonionic sugar-based
thio-containing amphiprotic surfactants would be expected to have certain scientific
significance and applicable prospects.
(4f)
(4e)
(4b)
(4d)
(4a)
100um
100um
100um
(4c)
100um
100um
100um
Fig. 6 Liquid crystal texture of alkyl β-D-thioglucopyranoside (4a ~ 4f)
4. Conclusions
In the paper, peracetylglucose (2) was coupled with mercaptans under the
catalysis of Lewis acid BF3·Et2O, followed by deprotection to obtain alkyl

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β-D-thioglucopyranosides (4a ~ 4f). The 1,2-trans β-D-thioglucopyranosides were
1
characterized by H NMR technology, the coupling constants (J1,2) of alkyl
S-glucopyranosides were at the range of 9.7–9.9 Hz, the values were obviously higher
than that of alkyl O-glucopyranosides [44].
With the prepared sugar-based sulfur-containing amphiphiles in hands, their HLB
number, logP value, water solubility, surface tension, foam property, emulsifying
property, focal-conic fan texture and so on were investigated. The results indicated as
follows: (1) A new method was introduced to calculate reasonably the related HLB
number (11.7 (4a, n = 6) → 9.0 (4f, n = 12)) since sulfur atom had special
electronegativity and weaker hydrophilicity. (2) The HLB number of alkyl
β-D-thioglucopyranosides (4a ~ 4f) decreased gradually as the related logP value
increased with increasing the alkyl chain length. (3) The related solubility in water
and ethanol gradually decreased with increasing the alkyl chain length, and alkyl
β-D-thioglucopyranosides were not soluble in water while the alkyl chain length n ≥
10. (4) Octyl β-D-thioglucopyranoside (4c) and nonyl β-D-thioglucopyranoside (4d)
had excellent foaming ability and foam stability. (5) Alkyl β-D-thioglucopyranosides
(4a ~ 4d) reduced the surface tension of their aqueous solution, octyl
β-D-thioglucopyranoside (4c) and nonyl β-D-thioglucopyranoside (4d) had relative
strong surface activity. (6) Octyl β-D-thioglucopyranoside (4c) had the strongest
foaming ability and better foaming stability; nonyl β-D-thioglucopyranoside (4d) had
the strongest emulsifying properties for both n-octane/water system and toluene/water
system. (7) Alkyl β-D-thioglucopyranosides (4a ~ 4f) were observed to have the

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thermotropic liquid crystalline behavior.
Indeed, sulfur, as a functional heteroatom, linked hydrophilic glucopyranosyl
group and hydrophobic alkyl group so as to construct the S-glucopyranoside and
endue a lot of interesting structure-property relationships, which is of course different
from O-glucopyranoside involving in preparation [52], structure modification,
characterization, amphilicity [53, 54], theoretical simulation [55], water solubility,
surface activity [10, 56, 57], thermotropic and/or lyotropic liquid crystalline [1, 58],
phase diagram [59, 60], functional materials, chemical technology and engineering
optimization, bioactivity [61], protein-glycoside interaction [62], biodegradation [63],
biotoxicity [11, 13], eco-environmental concerns [64] and so on. Although there have
been a number of progressive investigations, it is particularly for the necessity that
more efforts should be made on their scientific research, practical advanced
application and potential commercial value as well.
Acknowledgments
This work was supported by the National Natural Science Foundation of China
(grant numbers 21643010) and Hunan 2011 Collaborative Innovation Center of
Chemical Engineering & Technology with Environmental Benignity and Effective
Resource Utilization.
Elemenary Supporting Information (ESI) to this article can be found online at ….
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