A Convenient Trimethylsilylthioxy-Dehalogenation Reaction for the Preparation of Functionalized Thiols

Full text of DOI:10.1021/jo990076h

J . Org. Chem. 1999, 64, 4959-4961
4959
3 4
(Me SiS Bu
N , 1),7 generated in situ by adding a
-
+
A Con ven ien t
solution of tetrabutylammonium fluoride (TBAF) to hex-
amethyldisilathiane in THF, reacts rapidly with a variety
of alkyl bromides and chlorides at ambient temperature
Tr im eth ylsilylth ioxy-Deh a logen a tion
Rea ction for th e P r ep a r a tion of
F u n ction a lized Th iols
(
eq 1). Upon aqueous workup or filtration through a silica
J un Hu and Marye Anne Fox*,†
†
Department of Chemistry and Biochemistry, University of
Texas at Austin, Austin, Texas 78712, and Department of
Chemistry, North Carolina State University,
Raleigh, North Carolina 27695
Received J anuary 15, 1999
gel column, the corresponding thiols are produced in
excellent yields (Table 1).
We report a new synthetic method for thiol synthesis
and its application in the in situ generation of self-
assembled thiolate monolayers on noble metals. Thiols
are versatile synthetic intermediates and are considered
To the best of our knowledge, this procedure represents
the mildest available method for thiol synthesis. In
addition, it can be conveniently carried out with common
synthetic reagents in about 1 h of operation. Because the
reaction is conducted under near neutral reaction condi-
tions for a short period of time, autoxidation of thiol
products to disulfides and/or sulfonic acids becomes less
severe compared to the methodologies that require basic
hydrolysis. Furthermore, we found that this procedure
can be used to generate highly electron deficient thiol
derivatives, which are particularly difficult to synthesize
because of the strong tendencies for intramolecular single
electron-transfer oxidation of key thiolate intermediates
1
crucial in many biological processes. Long-standing
interest in thiol-containing compounds has recently been
stimulated by their utility in the formation of self-
assembled monolayers (SAMs) of alkanethiolates on
2
noble metal surfaces. Synthesis and characterization of
functionalized SAMs is becoming increasingly important
as a vehicle for preparing well-ordered thin films and for
using such SAMs in interfacial design and in materials
3
fabrication. For some time, our group has been inter-
3
g,4
ested in the photochemical properties of SAMs,
and
the ability to prepare the required thiols and monolayers
in situ would simplify the preparation methods now being
used.5
8
in the reactions. For example, we have been able to apply
this method to generate the highly functionalized thiol
2
(eq 2) without the complications encountered using
Accordingly, we sought a new synthetic method for
generating functionalized thiols. It is well-known that
methods for direct mercapto-dehalogenation of alkyl
halides usually suffer from secondary alkylations to form
dialkyl sulfide byproducts. An ideal procedure for thiol
synthesis should thus involve an efficient transformation
to form a protected but easily activated thiol derivative
and should have a subsequent deprotection step that can
be achieved without the strongly acidic or basic conditions
6
associated with more conventional methods. We have
found that tetrabutylammonium trimethylsilylthiolate
*
To whom correspondence should be addresssed.
Current address: Department of Chemistry, North Carolina State
†
University, Raleigh, NC 27695-8204.
1) Wardell, J . L. In The Chemistry of the Thiol Group; Patai, S.,
Ed.; Wiley: London, 1974; p 179.
2) (a) DuBois, L. H.; Nuzzo, R. G. Annu. Rev. Chem. Phys. 1992,
currently prevalent methods that involve thiolate inter-
mediates, e.g., decomposition of the substrate in basic
conditions presumably initiated by reduction of the
(
(
4
4
3, 437. (b) Nuzzo, R. G.; Allara, D. L. J . Am. Chem. Soc. 1983, 105,
481.
nitrobenzene group. The synthesis takes place efficiently
-
3
here because the intended substitution by Me SiS
(3) (a) Ulman, A. Chem. Rev. 1996, 96, 1533. (b) Bain, C. D.;
Troughton, E. B.; Tao, Y.-E.; Evall, J .; Whitesides, G. M.; Nuzzo, R.
G. J . Am. Chem. Soc. 1989, 111, 321. (c) Abbott, N. L.; Folkers, J . P.;
Whitesides, G. M. Science 1992, 257, 1380. (d) Laibinis, P. E.;
Whitesides, G. M.; Allara, D. L.; Tao, Y.-T.; Parikh, A. N.; Nuzzo, R.
G. J . Am. Chem. Soc. 1991, 113, 7152. (e) Chidsey, C. E. D.; Liu, G.;
Scoles, G.; Wang, J . Langmuir 1990, 6, 682. (f) Wollman, E. W.; Kang,
D.; Frisbie, C. D.; Lorkovic, I. M.; Wrighton, M. S. J . Am. Chem. Soc.
competes favorably with the reduction of the electron
deficient nitrobenzene group.
Although reactions of hexamethyldisilathiane with
alkyl halides have been studied previously, the use of this
9
reagent for thiol sythesis is unprecedented. Abel et al.
reported that dialkyl sulfides are produced when hex-
amethyldisilathiane is allowed to react with activated
alkyl halides. They also demonstrated that alkyl tri-
1
1
994, 116, 4396. (g) Wolf, M. O.; Fox, M. A. J . Am. Chem. Soc. 1995,
17, 1845.
(
4) Fox, M. A.; Wooten, M. D. Langmuir 1997, 26, 77099.
(5) Tour, J . M.; J ones, L. J ., II; Pearson, D. L.; Lamba, J . J . S.;
Burgin, T. P.; Whitesides, G. M.; Allara, D. L.; Parikh, A. N.; Atre, S.
V. J . Am. Chem. Soc. 1995, 117, 9529.
(7) Prakash, G. K. S.; Yudin, A. K.; Deffieux, D.; Olah, G. A. Synlett
(
6) (a) The thiourea method: Frank, R.; Smith, P. V. J . Am. Chem.
1996, 151.
Soc. 1946, 68, 2103. (b) The thiol ester method: see ref 1. (c) The
thiocyanate method: The Chemistry of Cyanates and Their Thio
Derivatives; Patai, S., Ed.; Wiley: New York, 1977; p 819.
(8) Hu, J .; Fox, M. A. Unpublished results.
(9) Abel, E. W.; Armitage, D. A.; Bush, R. P. J . Chem. Soc. 1964,
2455.
1
0.1021/jo990076h CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/02/1999

4
960 J . Org. Chem., Vol. 64, No. 13, 1999
Notes
Ta ble 1. Tr im eth ylsilylth ioxy-Deh a logen a tion of
Br om id es a n d Ch lor id es w ith Tetr a bu tyla m m on iu m
F lu or id e a n d Hexa m eth yld isila th ia n e
F igu r e 1. Cyclic voltammograms of 1.0 mM potassium
ferricyanide obtained using SAM-modified gold surfaces (ap-
2
proximately 1.0 cm ) as the working electrodes: (a) with a
SAM electrode formed from a 1-decanethiol solution; (b) with
a SAM formed from a heated mixture of 1-decanethiol and
TBAF; (c) with a SAM formed from a heated synthetic mixture
of 1-decanethiol starting with bromodecane. The measure-
ments were performed in a three-electrode cell using platinum
as the counter electrode and Ag/AgCl as the reference elec-
trode. Potassium chloride (1.0 M) was used as the supporting
electrolyte and the sweeping rate was 100 mV/s.
a
GC yield. b Isolated yield.
methylsilathiane is an intermediate in this reaction by
allowing it to react with an excess of alkyl halide. Shiao
et al. also reported a procedure for in situ generation of
The scope of the new synthetic method was examined
with several different types of electrophiles as shown in
Table 1. Because most thiols are unstable toward disul-
fide formation, our method provides a quick and conve-
nient access to fresh thiols. It is usually advantageous
to use the thiol product in the synthetic mixture without
separation and purification. This possibility was explored
in the formation of self-assembled 1-decanethiol mono-
layer on gold (eq 3).
-
+ 10
3
sodium trimethylsilylthiolate (Me SiS Na ). This re-
agent reacts with alkyl halides to produce exclusively
dialkyl sulfides although it also reduces nitrobenzene
derivatives to aromatic amines quite effectively.10 We
found that the use of TBAF in generating the trimeth-
ylsilylthiolate anion greatly improves the nucleophilicity
of the reagent so that it reacts rapidly even at low
temperatures, effecting a significant improvement in
selectivity. If the reaction is carried out using a suspen-
sion of sodium methoxide in THF as the initial desilyla-
tion agent, a mixture of thiol and dialkyl sulfide may be
produced (for 1-bromodecane, a roughly 3:2 mixture of
thiol and sulfide by gas-liquid chromatography (GLC)).
In a typical preparation (eq 1), a stirred solution of
alkyl bromide (about 0.5 M in freshly distilled THF) was
cooled to -10 °C, and hexamethyldisilathiane (1.2 equiv,
Aldrich) and TBAF (1.1 equiv, 1.0 M solution in THF with
Indeed, as indicated by grazing angle reflectance FT-
IR spectroscopy12 and by contact angle measurements,
a well-ordered SAM of 1-decanethiol is formed at room
temperature from a diluted synthetic mixture starting
from 1-bromodecane. However, further examination of
the SAM by cyclic voltammetry (CV) revealed that the
faradaic current was only incompletely blocked by the
decanethiolate monolayer prepared by in situ generation
of the thiol, unlike a SAM prepared by treating a fresh
gold surface with decanethiol solution. This result indi-
cates the important role of surface deposition rate in
accessing well-ordered SAMs.
13
5
% water, Aldrich) were added. The resulting reaction
mixture was allowed to warm to room temperature while
being stirred. For bromides bearing highly electron-
withdrawing groups, the reaction was shielded from room
light in order to avoid photoinduced side reactions. After
the disappearance of the bromide (about 20 min at
ambient temperature, as observed by thin-layer chroma-
tography (TLC) or GLC monitoring), the reaction mixture
was diluted with a common organic solvent such as
diethyl ether or methylene chloride and washed with
aqueous ammonium chloride (sat.). A reasonably clean
The most likely competitor to uniform thiolate deposi-
tion is the physical adsorption of tetrabutylammonium
bromide on the gold surface,14 which blocks the chemical
1
1
thiol sample can be obtained by evaporating the solvent.
Vacuum distillation or flash column chromatography can
be performed, depending on the stability of the thiol
product, to further purify the crude product.
(
12) Allara, D. L. In Characterization of Organic Thin Films; Ulman,
A., Ed.; Manning Publications: Greenwich, CT, 1995; p 57.
13) Laibinis, P. E.; Whitesides, G. M.; Allara, D. L.; Tao, Y.-T.;
(
(
10) Shiao, M.-J .; Lai, L.-L.; Ku, W.-S.; Lin, P.-Y.; Hwu, J . R. J . Org.
Chem. 1993, 58, 4742.
11) Disulfides are observed as impurities in the crude thiol products
3-10% for reactions of about 0.5 mmol scales). They are most likely
formed by autooxidation during the workup and isolation process.
Parikh, A. N.; Nuzzo, R. G. J . Am. Chem. Soc. 1991, 113, 7152. Contact
angles measured by a sessile drop technique for a bare polycrystalline
gold surface, for a preformed 1-decanethiol SAM, and for an in situ
prepared SAM from 1-bromodecane are 58 ( 1.9°, 96.4 ( 3.7°, and
94.1 ( 1.8°, respectively.
(
(

Notes
J . Org. Chem., Vol. 64, No. 13, 1999 4961
interaction of the gold surface with a nearby incoming
thiol. By preparing the SAM in situ under more rigorous
conditions (under reflux for several hours), the faradaic
current exhibited in the CV is greatly reduced, consistent
with better packing in the monolayer and with more
complete SAM coverage of the surface (Figure 1). If a
SAM is generated from a reaction mixture that has been
washed several times with distilled water to remove the
tetrabutylammonium salt, its CV characteristics are
identical to that of a well-ordered SAM deposited from a
thiol solution. The above observation further supports the
supposition that tetrabutylammonium salts may cause
increased defects in the in situ generated SAM, but that
annealing can heal these defects, at least partially.
Ack n ow led gm en t. This work was supported by the
U.S. Dept. of Energy. We also thank Professor J . K.
Whitesell and Dr. Scott Reese for helpful discussion.
Su p p or tin g In for m a tion Ava ila ble: Compound charac-
terization data and copies of NMR spectra for Table 1, entries
7
and 9. This material is available free of charge via the
Internet at http://pubs.acs.org.
(14) Fink, J .; Kiely, C. J .; Bethell, D.; Schiffrin, D. J . Chem. Mater.
1
998, 10, 922.
J O990076H