3-(2-aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione as an ecofriendly sulphur transfer agent to prepare alkanethiols in high yield and high purity

Article abstract of DOI:10.3390/molecules14114634

A new process is described for preparing very pure linear alkanethiols and linear α,ω-alkanedithiols using a sequential alkylation of the title compound, followed by a ring closure to quantitatively give the corresponding 3-methyl[1,3]thiazolo[3,2-a]-[3,1

Full text of DOI:10.3390/molecules14114634

Molecules 2009, 14, 4634-4643; doi:10.3390/molecules14114634
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
3-(2-Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione as an
Ecofriendly Sulphur Transfer Agent to Prepare Alkanethiols in
High Yield and High Purity
Mohammed Amine Mehdid 1, Ayada Djafri 1, Christian Roussel 2 and Federico Andreoli 2,*
1
Laboratoire de synthèse organique appliquée, Département de Chimie, Faculté de Sciences,
Université d’Oran-es-Senia, Algeria; E-Mails: mmehdid@yahoo.fr (M.A.M.);
djafriayada@yahoo.fr (A.D)
2
ISM2, Chirosciences, Université Paul Cézanne Aix-Marseille III, 13397 Marseille CEDEX 20,
France; E-Mail: christian.roussel@univ-cezanne.fr (C.R.)
* Author to whom correspondence should be addressed; E-Mail: federico.andreoli@univ-cezanne.fr.
Received: 29 October 2009; in revised form: 10 November 2009 / Accepted: 11 November 2009 /
Published: 12 November 2009
Abstract: A new process is described for preparing very pure linear alkanethiols and linear
α,ω-alkanedithiols using a sequential alkylation of the title compound, followed by a ring
closure to quantitatively give the corresponding 3-methyl[1,3]thiazolo[3,2-a]-
[3,1]benzimidazol-9-ium salt and the alkanethiol derivative under mild conditions. The
alkanethiol and the heteroaromatic salt are easily separated by a simple extraction process.
The intermediate thiazolium quaternary salts resulting from the first reaction step can be
isolated in quantitative yields, affording an odourless protected form of the thiols.
Keywords: thiols; dithiols; sulphur transfer; thiazoline-2-thione
Introduction
Long-chain n-alkanethiols and α,ω-alkanedithiols are valuable compounds in material sciences due
to their ability to bind on gold surfaces [1-8]. In relation with the demand for very pure n-alkanethiols
and α,ω-alkanedithiols, new methods for the synthesis of these molecules have been developed,
furnishing good alternatives to classical ones [9-11]. Among them, the trimethylsilylthioxy-

Molecules 2009, 14
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dehalogenation reaction reported by Hu and Fox [12], the direct synthesis from alcohols by Bandgar,
Sadavarte and Uppalla [13], and the SmI2-promoted reductions of sodium alkyl thiosulfates and alkyl
thiocyanates of Zhan, Lang, Liu and Hu [14], give alkanethiols in average to good yields; however, for
all these methods, distillation or column chromatography is needed to further purify the final product.
The one pot conversion of alkyl halides into thiols proposed by Molina, Alajarin and Vilaplana [15]
doesn’t require final purification steps, but suffers from low yields (lower than 66%) when applied to
the synthesis of long chain n-alkanethiols.
Moreover, it must be stressed that thiols easily undergo oxidation to disulphides under ambient
conditions. Protecting groups are thus used to grant long term stability to derivatives, implying
development of protection-deprotection procedures [16-20] with consequent loss of yield.
Herein we report a new n-alkanethiol and linear α,ω-alkanedithiol synthesis which involves the
formation of a (bis-)thiazolium salt, starting from 3-(2-aminophenyl)-4-methyl-1,3-thiazole-2(3H)-
thione (1) and the corresponding (di)halide. The reactions are carried out under mild conditions and no
inert conditions are needed; the final products are recovered in their pure form by simple extraction.
Results and Discussion
3-(2-Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione (1) represents a cornerstone for different
projects in progress in our laboratory [21-25]. Firstly described by Bellec et al. [26], the synthetic
route to 1 starts from readily available material (CS2, chloracetone and phenylene-1,2-diamine); this
synthesis has been further optimised, leading to crystallised thiazoline-2-thione 1 in 75% isolated
yield. We have described that the reaction of 1 with methyliodide gave a salt 2 (R = Me, Scheme 1)
which was cleanly transformed into thiazolobenzimidazole affording a new and efficient access to that
aromatic tricyclic framework [22]. The only by-product was methanethiol, which escaped from the
reaction medium and was not characterized. If one considers the two step process described in Scheme
1, the thiazoline-2-thione 1 is thus acting as a sulphur transfer agent which mediates the transformation
of an alkyl halide into an alkanethiol. The sulphur transfer is occurring through salt 2, which can be
considered as a protected form of the alkanethiol. We thus wondered if this procedure might lead to a
general and clean synthesis of long-chain n-alkanethiols.
A series of different linear alkyliodides was reacted with thiazolinethione 1 to produce the derived
thiazolium iodides 2 in high yield. In a second step, under heating in refluxing methanol, the
thiazolium iodides 2 were quantitatively transformed in a known thiazolobenzimidazolium salt and the
corresponding thiols (Scheme 1).
Scheme 1. n-Alkanethiols synthesis via thiazolium iodides.
S
S
S
R
I-
NH+
S
S
N+
N
N
I-
CH3OH
R
I
+
R
SH
3h, 90°C
NH2
NH2
12h, reflux
3a-e
1
2a-e

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The results obtained are summarized in Table 1.
Table 1. Isolated yields in thiazolium iodides and thiols.
Reagent
Thiazolium salt Yield (%)
Thiol
3a
Yield (%)
CH3(CH2)6I
CH3(CH2)8I
CH3(CH2)9I
CH3(CH2)11I
CH3(CH2)17I
2a
2b
2c
2d
2e
96
96
94
93
98
90
92
94
91
92
3b
3c
3d
3e
In the first step, the solvent free reaction of thiazoline-2-thione 1 with an excess of the
corresponding alkyliodide (Scheme 1) generates the respective thiazolium iodides 2. TLC monitoring
confirmed that, for all entries, the starting material 1 completely disappeared after 3 h at 90 °C. Salts 2
were then isolated in very good yields (Table 1) by simple filtration over silica gel and fully
characterised. The purification step allows one to recover and to reuse all the excess of alkyliodide, so
that the molar ratio 1/(alkylating agent) can be brought closer to 1/1. Moreover, removal of the excess
halide from the medium prevents the formation of unwanted dialkylsulphides, once the thiol is formed
in the second step. Last but not least, iodides 2 are stable and odourless compounds that can be stored
at 3-4 °C without any risk of alteration, thus the thiazoline moiety acts as a protecting group for
the thiol.
Thiazolium iodides 2 are then easily converted by cyclization in methanol under reflux into the
thiazolobenzimidazolium iodide in 12 h, releasing the corresponding thiol (second step, Scheme 1).
Thiols 3a-e were isolated as pure compounds in yields higher than 90% (Table 1) by simple extraction
with Et2O. No formation of disulphide by-product was observed in the final products. However when
the reaction was performed using various substituted benzylchlorides as alkylating agent for 1 a
mixture of substituted benzylmercaptans and substituted dibenzyldisulphides was obtained (data
not shown).
The good results obtained for n-alkanethiols prompted us to apply this method to the synthesis of
α,ω-alkanedithiols. In this case, the reaction conditions were changed, due to the need to obtain bis-
thiazolium salts. Thiazoline-2-thione 1 was then reacted with 1/2 mole of α,ω-alkyldiiodides in
chloroform under reflux (Scheme 2).
Scheme 2. Dithiols synthesis via bis-thiazolium diiodides.
S
S
S
S
I-
NH+
S
N+
N+
N
N
S
S
HS
+
SH
n
I
I
n
CH3OH
n
I-
I-
NH2
12h, reflux
CHCl3, reflux, 24h
NH2
H2N
3f-h
2f-h
1

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Once again, the complete disappearance of the starting product was monitored by TLC. Two
different work ups were successively used to isolate the obtained products (see Experimental section).
1H-NMR spectra were recorded for each compound 2f-h, confirming the presence of the corresponding
bis-thiazolium diiodides as unique compounds. The salts 2f-h were then fully characterised and the
respective yields are reported in Table 2. It should be noted that bis-thiazolium diiodides 2 might be
obtained as a mixture of diastereomers (meso and d, l) since the starting thiazoline-2-thione 1 is chiral
[10]. A detailed analysis of this mixture was beyond the scope of this paper since the cyclization step
leading to α,ω-alkanedithiols yielded the same achiral compounds starting from either diastereomer.
Table 2. Isolated yields of bis-thiazolium diiodides and α,ω-alkanedithiols.
Reagent Thiazolium salt Yield (%) Thiol Yield (%)
I(CH2)3I
I(CH2)4I
I(CH2)5I
2f
2g
2h
94
95
89
3f
3g
3h
91
90
92
Like thiazolium salts 2a-e, bis-thiazolium salts 2f-h can be stored at 3-4°C without any risk of
alteration and show all the advantages mentioned for 2a-e. The same procedure and work up used to
obtain thiols is then applied to the synthesis of α,ω-alkanedithiols: after 2h under reflux in MeOH, the
cyclization to thiazolobenzimidazole is complete and α,ω-alkanedithiols 3f-3h are recovered by simple
extraction with Et2O. It must be stressed that also in this case no formation of by-products derived
from sulphur oxidation was observed.
Experimental
General
1H-NMR spectra were recorded at 500, 300 or 200 MHz and 13C-NMR spectra at 125, 75 or
50 MHz on Bruker Avance DRX-500, DPX-300 or 200 instruments, respectively. Chemical shifts are
reported in ppm with the signal for residual solvent as internal standard. J values are reported in Hz.
High resolution mass spectra were performed on Q-STAR Elite spectrometer. Melting points were
measured using a Büchi Melting Point B-545 apparatus. Filtrations through silica gel were performed
with silica gel 60 (230-400 mesh). TLCs were carried out on Merck 60F254 silica plates. 3-(2-
Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione (1) was prepared according to reference [22]. All
the halogen compounds were commercially available (Sigma-Aldrich, Alfa Aesar).
General procedure for the synthesis of monothiazolium iodides 2a-e
3-(2-Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione (1, 300 mg, 1.35 mmol) was suspended in
the corresponding iodoalkane (for 2a: n-heptyliodide, 2.4 mL, 14.64 mmol; for 2b: n-nonyliodide,
2.8 mL, 14.17 mmol; for 2c: n-decyliodide, 2.8 mL, 13.12 mmol; for 2d: n-dodecyliodide, 2.8 mL,
11.35 mmol; for 2e: n-octadecyliodide, 3.8 g, 9.99 mmol) and the mixture stirred at 90 °C. After 3 h,
the mixture is cooled to r.t. and CH2Cl2 (3 mL) is added to completely dissolve the precipitate formed.
The solution is filtered on silica gel to remove the excess of alkyl halide (using CH2Cl2). Then the

Molecules 2009, 14
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silica is washed with MeOH and the corresponding thiazolium iodide is recovered after evaporation of
the solvent.
3-(2-Aminophenyl)-2-(heptylthio)-4-methylthiazol-3-ium iodide (2a): Yield: 96% (581 mg, orange
1
solid); mp: 53-55°C; H-NMR (300 MHz, CDCl3) δ = 0.85 (t, 3H, J = 6.7; CH3), 1.25-1.47 (m, 8H;
4(CH2)), 1.77-1.88 (m, 2H; CH2), 2.26-2.27 (d, 3H, J = 1.0; CH3), 3.27-3.59 (m, 2H; SCH2), 4.79 (s,
2H; NH2), 6.79-6.84 ( m, 1H; Ar), 6.93-7.00 (m, 2H; Ar), 7.33-7.38 (m, 1H; Ar), 7.92 (q, 1H, J = 1.0;
=CH); 13C-NMR (75 MHz, CDCl3) δ = 14.12, 14.37, 22.59, 27.62, 28.75, 28.83, 31.47, 36.82, 118.37,
+
118.53, 118.64, 118.83, 126.87, 133.19, 143.16, 145.67, 177.91; HRMS m/z calcd C17H25N2S2 [M-
I]+: 321.1454, found: 321.1455.
3-(2-Aminophenyl-2-(nonylthio)-4-methylthiazol-3-ium iodide (2b): Yield: 96% (617 mg, orange
1
solid); mp: 51-53°C; H-NMR (300 MHz, CDCl3) δ = 0.85 (t, 3H, J = 6.7; CH3), 1.23-1.45 (m, 12H;
6(CH2)), 1.76-1.87 (m, 2H; CH2), 2.26 (d, 3H, J = 0.9; CH3), 3.26-4.11 (m, 4H; SCH2+NH2), 6.78-6.84
( m, 1H; Ar), 6.93-7.00 ( m, 2H; Ar), 7.32-7.38 ( m, 1H; Ar), 7.93 (q, 1H, J = 0.9; =CH); 13C-NMR (75
MHz, CDCl3) δ = 14.18, 14.35, 22.71, 27.62, 28.87, 29.09, 29.23, 29.35, 31.87, 36.81, 118.37, 118.52,
+
118.65, 118.88, 126.86, 133.17, 143.16, 145.65, 177.88; HRMS m/z calcd C19H29N2S2 [M-I]+:
349.1767, found: 349.1767.
3-(2-Aminophenyl)-2-(decylthio)-4-methylthiazol-3-ium iodide (2c): Yield: 94% (622 mg, orange
solid); mp: 52-54 °C; 1H-NMR (300 MHz, CDCl3) δ = 0.85 (t, 3H, J = 6.6; CH3), 1.22-1.44 (m, 14H;
7(CH2)), 1.76-1.86 (m, 2H; CH2), 2.26 (d, 3H, J = 0.7; CH3 ), 3.26-3.58 (m, 2H; SCH2), 4.79 (s, 2H;
NH2), 6.78-6.83 (m, 1H; Ar), 6.93-7.01 (m, 2H; Ar), 7.32-7.37 (m, 1H; Ar), 7.95 (q, 1H, J = 0.7;
13
=CH); C-NMR (75 MHz, CDCl3) δ = 14.17, 14.34, 22.71, 27.60, 28.86, 29.07, 29.31, 29.37, 29.50,
31.90, 36.79, 118.35, 118.50, 118.63, 118.97, 129.85, 133.14, 143.15, 145.59, 177.81; HRMS m/z
+
calcd C20H31N2S2 [M-I]+: 363.1923, found: 363.1922.
3-(2-Aminophenyl)-2-(dodecylthio)-4-methylthiazol-3-ium iodide (2d): Yield: 93% (651 mg, orange
1
solid); mp: 50-52°C; H-NMR (300 MHz, CDCl3) δ = 0.86 (t, 3H, J = 6.7; CH3), 1.23-1.45 (m, 18H;
9(CH2)), 1.77-1.88 (m, 2H; CH2), 2.27 (d, 3H, J = 0.7; CH3), 3.27-3.60 (m, 2H; SCH2), 4.81 (s, 2H;
NH2), 6.79-6.84 (m, 1H; Ar), 6.93-6.99 (m, 2H; Ar), 7.33-7.39 ( m, 1H; Ar), 7.90 (q, 1H, J = 0.7;
13
=CH); C-NMR (75 MHz, CDCl3) δ = 14.22, 14.36, 22.77, 27.64, 28.90, 29.11, 29.41 (2C), 29.59,
29.69 (2C), 31.99, 36.84, 118.37, 118.50, 118.64, 118.81, 126.87, 133.18, 143.20, 145.68, 177.96;
+
HRMS m/z calcd C22H35N2S2 [M-I]+: 391.2236, found: 391.2237.
3-(2-Aminophenyl-2-(octadecylthio)-4-methylthiazol-3-ium iodide (2e): Yield: 98% (797 mg, orange
solid); mp: 51-53 °C; 1H-NMR (300 MHz, CDCl3) δ = 0.86 (t, 3H, J = 6.7; CH3), 1.18-1.46 (m, 30H;
15(CH2)), 1.46-1.78 (m, 2H; CH2), 2.27-2.28 (d, 3H, J = 0.9; CH3), 3.27-3.61 (m, 2H; SCH2), 4.78 (s,
2H; NH2), 6.79-6.85 (m, 1H; Ar), 6.93-6.99 (m, 2H; Ar), 7.34-7.39 (m, 1H; Ar), 7.88 (q, 1H, J = 0.9;
13
=CH); C-NMR (75 MHz, CDCl3) δ = 14.24, 14.40, 22.80, 27.65, 28.92, 29.13, 29.44, 29.48, 29.62,
29.73, 29.77 (brs), 29.81 (brs), 32.04, 36.88, 118.36, 118.54, 118.61 (2C), 126.87, 133.23, 143.17,
+
145.77, 178.05; HRMS m/z calcd C28H47N2S2 [M-I]+: 475.3175, found: 475.3166.

Molecules 2009, 14
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Procedure for the synthesis of bis-thiazolium diiodides 2f and 2g
3-(2-Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione (1, 200 mg, 89.96 mmol) was dissolved in
CHCl3 (5 mL), then the corresponding α,ω-diiodide is added (for 2f: 1,3-diiodopropane, 52 μL, 0.5 eq;
for 2g: 1,4-diiodobutane, 59 μL, 0.5 eq) and the solution refluxed under magnetic stirring. After 24 h,
the formed precipitate is filtered and washed with CHCl3 to yield the corresponding bis-thiazolium
diiodide.
2,2'-(Propane-1,3-diyldisulfanediyl)bis[3-(2-aminophenyl)-4-methyl-1,3-thiazol-3-ium] diiodide (2f):
1
Yield: 94% (313 mg, pale yellow solid); mp: 178-180°C (mixt.); H-NMR (500 MHz, CD3OD)
δ = 2.25 (d, 6H, J = 0.9; 2CH3), 2.45-2.52 (m, 2H; CH2), 3.62 (t, 4H, J = 7.2; 2(SCH2)), 6.80-6.83 (m,
2H; Ar), 6.99-7.01 (m, 2H; Ar), 7.18-7.21 (m, 2H; Ar), 7.36-7.40 (m, 2H; Ar), 7.86 (q, 2H, J = 0.9;
13
2(=CH)); C-NMR (125 MHz, CDCl3) δ = 13.90 (2C), 27.31, 35.00 (2C), 118.55 (2C), 118.63 (2C),
118.79 (2C), 119.67 (2C), 128.53 (2C), 134.19 (2C), 145.26 (2C), 148.12 (2C), 179.08 (2C); HRMS
m/z calcd C23H26N4S42+ [M-2I]2+: 243.0515, found: 243.0519.
2,2'-(Butane-1,4-diyldisulfanediyl)bis[3-(2-aminophenyl)-4-methyl-1,3-thiazol-3-ium] diiodide (2g):
1
Yield: 95% (322 mg, pale yellow solid); mp: 259-261 °C (mixt.); H-NMR (500 MHz, CD3OD)
δ = 2.04-2.09 (m, 4H; 2(CH2)), 2.25 (d, 6H, J = 1.1; 2CH3), 3.47-3.54 (m, 4H; 2(SCH2)), 6.79-6.85 (m,
2H; Ar), 6.98-7.02 (m, 2H; Ar), 7.13-7.16 (m, 2H; Ar), 7.35-7.41 (m, 2H; Ar), 7.83 (q, 2H, J = 1.1;
13
2(=CH)); C-NMR (125 MHz, CDCl3) δ = 13.83 (2C), 27.74 (2C), 35.87 (2C), 118.10 (2C), 118.71
(2C), 118.87 (2C), 119.73 (2C), 128.39 (2C), 134.21 (2C), 145.27 (2C), 148.14 (2C), 179.61 (2C);
HRMS m/z calcd C24H28N4S42+ [M-2I]2+: 250.0593, found: 250.0586.
Procedure for the synthesis of bis-thiazolium diiodide 2h
3-(2-Aminophenyl)-4-methyl-1,3-thiazole-2(3H)-thione (1, 200 mg, 89.96 mmol) was dissolved in
CHCl3 (5 mL), then 1,5-diiodopentane (67 μL, 0.5 eq) is added and the solution refluxed under
magnetic stirring. After 48 h, the solution is cooled to r.t. and CH2Cl2 (5 mL) is added. The solution is
filtered on silica gel to remove the excess of reactive (using CH2Cl2). Then the silica is washed with
MeOH and bis-thiazolium diiodide 2h is recovered after evaporation of the solvent.
2,2'-(Pentane-1,5-diyldisulfanediyl)bis[3-(2-aminophenyl)-4-methyl-1,3-thiazol-3-ium] diiodide (2h):
Yield: 89% (308 mg, orange solid); mp: 72-74°C (mixt.)C; 1H-NMR (200 MHz, CD3OD) δ = 1.58 (m,
2H; CH2), 1.89-2.03 (m, 4H; 2(CH2)), 2.24 (d, 6H, J = 1.0; 2CH3), 3.46 (t, 4H, J = 7.2; 2(SCH2)),
6.77-6.86 (m, 2H; Ar), 6.98-7.03 (m, 2H; Ar), 7.15-7.19 (m, 2H; Ar), 7.34-7.43 (m, 2H; Ar), 7.81 (q,
13
2H, J = 1.0; 2(=CH)); C-NMR (50 MHz, CD3OD) δ = 13.85 (2C), 28.20 (2C), 28.65, 36.47 (2C),
118.05 (2C), 118.69 (2C), 118.85 (2C), 119.78 (2C), 128.44 (2C), 134.14 (2C), 145.25 (2C), 147.97
(2C), 226.89 (2C); HRMS m/z calcd C25H30N4S42+ [M-2I]2+: 257.0671, found: 257.0662.
General procedure for the synthesis of n-alkanethiols
The corresponding thiazolium iodide (300 mg; 2a: 0.67 mmol; 2b: 0.63 mmol; 2c: 0.61 mmol; 2d:
0.58 mmol; 2e: 0.50 mmol) was dissolved in MeOH (2.5 mL) and the solution refluxed under magnetic

Molecules 2009, 14
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stirring. After 12 h, MeOH is evaporated and Et2O (20 mL) is added. The organic layer is washed with
5% HCl (3 × 15 mL) and brine (15 mL) and dried over MgSO4. Et2O is then evaporated to yield the
corresponding thiols.
1-Heptanethiol (3a) [27]: Yield: 90% (80 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 0.89 (t,
3H, J = 6.7; CH3), 1.26-1.43 (m, 9H; 4(CH2) + SH), 1.54-1.66 (m, 2H; CH2), 2.49-2.56 (m, 2H;
SCH2); 13C-NMR (75 MHz, CDCl3) δ = 14.20, 22.75, 24.81, 28.50, 28.89, 31.88, 34.21.
1-Nonanethiol (3b) [28]: Yield: 92% (93 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 0.88 (t,
3H, J = 6.6; CH3), 1.20-1.43 (m, 13H; 6(CH2) + SH), 1.55-1.65 (m, 2H; CH2), 2.48-2.55 (m, 2H;
SCH2); 13C-NMR (75 MHz, CDCl3) δ = 14.24, 22.81, 24.80, 28.53, 29.23, 29.40, 29.62, 32.01, 34.21.
1-Decanethiol (3c) [27]: Yield: 94% (100 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 0.87 (t,
3H, J = 6.6; CH3), 1.19-1.42 (m, 15H; 7(CH2) + SH), 1.55-1.65 (m, 2H; CH2), 2.48-2.55 (m, 2H;
SCH2); 13C-NMR (75 MHz, CDCl3) δ = 14.23, 22.81, 24.79, 28.53, 29.22, 29.44, 29.66, 29.69, 32.03,
34.20.
1-Dodecanethiol (3d) [27]: Yield: 91% (106 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 0.88
(t, 3H, J = 6.6; CH3), 1.19-1.43 (m, 19H; 9(CH2) + SH), 1.55-1.65 (m, 2H; CH2), 2.48-2.56 (m, 2H;
SCH2); 13C-NMR (75 MHz, CDCl3) δ = 14.26, 22.83, 24.81, 28.54, 29.23, 29.49, 29.67, 29.74, 29.78,
29.79, 32.06, 34.21.
1
1-Octadecanethiol (3e) [28]: Yield: 92% (131 mg, white solid); mp: 30-32°C; H-NMR (300 MHz,
CDCl3) δ = 0.88 (t, 3H J = 6.7; CH3), 1.19-1.43 (m, 31H; 15(CH2) + SH), 1.54-1.67 (m, 2H; CH2),
13
2.47-2.58 (m, 2H; SCH2); C-NMR (75 MHz, CDCl3) δ = 14.27, 22.85, 24.82, 28.54, 29.24, 29.52,
29.68, 29.75, 29.82 (3C), 29.85 (5C), 32.08, 34.22.
General procedure for the synthesis of α,ω-alkanedithiols
The corresponding bis-thiazolium diiodide (300 mg; 2f: 0.40 mmol; 2g: 0.40 mmol; 2h: 0.39 mmol)
of are dissolved in MeOH (10 mL) and the solution refluxed under magnetic stirring. After 12 h,
MeOH is evaporated and Et2O (20 mL) is added. The organic layer is washed with 5% HCl
(3 × 20 mL) and brine (15 mL) and dried over MgSO4. Et2O is then evaporated to yield the
corresponding dithiols.
1,3-Propanedithiol (3f) [28]: Yield: 91% (40 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 1.33
(t, 2H, J = 8.0; 2(SH)), 1.86-1.95 (m, 2H; CH2), 2.63-2.70 (m, 4H; 2(SCH2)); 13C-NMR (75 MHz,
CDCl3) δ = 23.01 (2C), 37.44.
1,4-Butanedithiol (3g) [27]: Yield: 90% (44 mg, colourless oil); 1H-NMR (300 MHz, CDCl3) δ = 1.35
13
(t, 2H, J = 7.8; 2(SH)), 1.70-1.76 (m, 4H; 2(CH2)), 2.51-2.58 (m, 4H; 2(SCH2)); C-NMR (75 MHz,
CDCl3) δ = 24.24 (2C), 32.70 (2C).

Molecules 2009, 14
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1
1,5-Pentanedithiol (3h) [28]: Yield: 92% (49 mg, colourless oil); H-NMR (300 MHz, CDCl3)
13
δ = 1.34 (t, 2H, J = 7.8; 2(SH)), 1.46-1.68 (m, 6H; 3(CH2)), 2.50-2.57 (m, 4H; 2(SCH2)); C-NMR
(75 MHz, CDCl3) δ = 24.60 (2C), 27.18, 33.54 (2C).
Conclusions
We have described a method that offers a new, mild, high yielding and particularly clean way to
synthesize n-alkanethiols and linear α,ω-alkanedithiols through a sulphur transfer reaction. In addition,
the possibility of isolating and storing the intermediate thiazolium salts offers a way to protect thiols in
an odourless form.
Acknowledgements
We thank the “Programme boursier intergouvernemental” B.A.F. (bourse algero-française) for
grants to Mohammed Amine Mehdid.
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27. National Institute of Advanced Industrial Science and Technology. For comparison of
spectroscopic data see: SDBS Web http://riodb01.ibase.aist.go.jp/sdbs/, accessed on 27 October
2009.
28. For
comparison
of
spectroscopic
data
see:
SIGMA-ALDRICH
website,
http://www.sigmaaldrich.com/, accessed on 13 November 2009.
Sample Availability: Samples of compounds 2a-h and 3a-h are available from the authors.
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
This article is an open-access article distributed under the terms and conditions of the Creative
Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).