Multistep synthesis on the surface of self-assembled thiolate monolayers on gold: Probing the mechanism of the thiazolium-promoted acyloin condensation

Full text of DOI:10.1021/ja970627q

6674
J. Am. Chem. Soc. 1997, 119, 6674-6675
Scheme 1
Multistep Synthesis on the Surface of
Self-Assembled Thiolate Monolayers on Gold:
Probing the Mechanism of the
Thiazolium-Promoted Acyloin Condensation
Kianoush Motesharei and David C. Myles*
Department of Chemistry & Biochemistry
UniVersity of California
Los Angeles, California 90095-1569
ReceiVed February 26, 1997
In this paper, we demonstrate the feasibility of multistep
synthesis on self-assembled thiolate monolayers on gold.1,2 We
use these synthetically modified self-assembled monolayers
(SAMs) to investigate the mechanism of an organic reaction:
the thiazolium-promoted acyloin condensation. Kinetic studies
by Breslow show that, under mildly basic conditions, the rate
of condensation is first order in thiazole (Scheme 1, pathway
A).3 Addition of ylide 2 to the aldehyde, followed by proton
transfer, affords the acyl anion equivalent 6 that undergoes
addition to a second aldehyde. After proton transfer, elimination
of thiazolium regenerates 2 and yields the acyloin product 8. A
second catalytic pathway (pathway B), involving the formation
of a thiazole dimer (3), typically observed under strongly basic
conditions, has also been suggested.4 After proton transfer, the
unlikely carbanionic intermediate 4 was proposed. Intermediate
4 can act as the acyl anion equivalent either by adding to a
second aldehyde (pathway B′) or alternatively (pathway B′′)
by undergoing cleavage to regenerate a thiazolium ylide and
acyl anion equivalent 6, as proposed by Breslow in pathway
A.
We chose to study the mechanism of the thiazolium-catalyzed
acyloin condensation in the context of thiazolium-functionalized
SAMs. Thiazolium-terminated thiols were synthesized via a
short sequence (Scheme 2). Mixed monolayers of thiazolium-
terminated thiol and octanethiol were formed by immersion of
polycrystalline gold on silicon in a solution containing oc-
tanethiol (30 mM) and the thiazolium-terminated thiol (2.5 mM).
We could then investigate the reaction of the surface-bound
thiazoliums with fluorescently5,6 labeled reactants from solution.
We synthesized fluorescently labeled intermediates and
substrates to investigate the mechanism of the acyloin condensa-
tion. To examine the catalytic activity of monothiazolium salts
(pathway A, Scheme 1), mixed monolayers of monothiazolium-
Scheme 2
functionalized decanethiol and octanethiol formed on gold films
(15) were immersed in 1.6 mM solutions of 9-anthraldehyde in
ethanol, acetone, or dichloromethane to synthesize enol inter-
mediate 17b. Excess triethylamine was added to each reaction
mixture to activate the catalyst. After the samples were warmed
(ca. 40-50 °C) for 3-12 h7 in ethanol, acetone, or dichlo-
romethane, the monolayers were removed and rinsed with pure
reaction solvent. Fluorescence spectroscopy was used to detect
the presence of the anthracyl moiety on the surface.8 In all
three solvents, a fluorescent intermediate, bonded covalently
to the surface, was detected.9 We attribute this to the formation
of the enol intermediate 17b (Scheme 3) on monolayer surface,
analogous to intermediate 6 (Scheme 1).
To examine formation of the thiazole dimer (analogous to 3)
and its role in the catalytic cycle, we synthesized an anthracene-
labeled thiazolium salt by alkylating 4-methylthiazole with
9-(chloromethyl)anthracene. Mixed monolayers of monothia-
zolium salts 15 were immersed in 1.0 mM solutions of the
anthracene labeled thiazolium salt in ethanol, acetone, or
dichloromethane. Excess triethylamine was added, and the
solutions were warmed for 12 h. Examination of the fluores-
cence of the monolayers, after removal from the reaction mixture
and rinsing showed the presence of the anthracene moiety on
the surface (18b) as evidenced by the fluorescence emission.
Formation of mixed monolayers of thiazole dimer prepared in
solution and octanethiol afforded SAMs that gave fluorescence
emission spectra that were identical to the previously obtained
(1) (a) Ulman, A. Ultrathin Organic Films from Langmuir Blodgett to
Self-Assembly; Academic Press: New York, 1991. (b) Bain, D. B.;
Troughton, E. B.; Tao, Y.-T.; Evall, J.; Whitesides, G. M.; Nuzzo, R. G. J.
Am. Chem. Soc. 1989, 111, 321. (c) Porter, M. D.; Bright, T. B.; Allara, D.
L.; Chidsey, C. E. D. J. Am. Chem. Soc. 1987, 109, 3559. (d) Ulman, A.;
Eilers, J. E.; Tillman, N. Langmuir 1989, 5, 1147. (e) Ulman, A.; Evans,
S. D.; Shindman, Y.; Sharma, R.; Eilers, J. E.; Chang, J. C. J. Am. Chem.
Soc. 1991, 113, 1499. (f) Zhang, L.; Lu, T.; Gokel, G. W.; Kaifer, A. E.
Langmuir 1993, 9, 786.
(2) For examples of chemical reactions on surface of SAMs, see: (a)
Muller, W. T.; Klein, T. L.; Less, T.; Clarke, J.; McEuwn, P. L.; Schultz,
P. G. Science 1995, 268, 272. (b) Balachander, N.; Sukenik, C. N. Langmuir
1990, 6, 1621. (c) Lander, L. M.; Brittain, W. J.; Tsukruk, V. Polym. Prepr.,
Am. Chem. Soc., DiV. Polym. Chem. 1994, 35, 488.
(3) See (and references therein): (a) Breslow, R.; Kool, E. Tetrahedron
Lett. 1988, 29, 635. (b) Breslow, R.; Kim, R. Tetrahedron Lett. 1994, 35,
699. (c) Breslow, R.; Schmuk, C. Tetrahedron Lett. 1996, 37, 8241.
(4) (a) Castells, J.; Lopez-Calahorra, F.; Geijo, F.; Perez-Dolz, R.;
Bassedas, M. J. Heterocycl. Chem. 1986, 23, 715. (b) Castells, J.; Lopez-
Calahorra, F.; Domingo, L. J. Org. Chem. 1988, 53, 4433. (c) Doughty,
M. B.; Risinger, G. E. Bioorg. Chem. 1987, 15, 1. (d) Lappert, M. F.;
Maskell, R. K. J. Chem. Soc., Chem. Commun. 1982, 580.
(5) Motesharei, K.; Myles, D. C. J. Am. Chem. Soc. 1994, 116, 7413.
(6) (a) Mathauer, K.; Frank, C. W. Langmuir 1993, 9, 3002. (b) Chen,
S. H.; Frank, C. W. Langmuir 1991, 7, 1719. (c) Chen, S. H.; Frank, C. W.
Langmuir 1989, 5, 978. (d) Hall, R. A.; Thistlethwaite, P. J.; Grieser, F.
Langmuir 1993, 9, 2128. (e) Stine, K. J.; Uang, J. Y.-J.; Dingman, S. D.
Langmuir 1993, 9, 2112. (f) Grabbe, E. S. Langmuir 1993, 9, 1574.
(7) The thermal stability of these monolayers has been examined by
surface-enhanced Raman spectroscopy. By following the change in the
integral of several signals, the half-life of an octanethiol monolayer in
ethanol at 40 °C was estimated to be ca. 30 h (R. L. Garrell and L. Yeager,
Department of Chemistry & Biochemistry, UCLA, unpublished results).
The thermal stability of thiolate monolayers has also been investigated by
wetting and X-ray photoelectron spectroscopy (Jennings, G. K.; Laibinis,
P. E. Langmuir, 1996, 12, 6173). These experiments suggest that the half-
life of thiolate monolayers in hydrocarbon solvent at 40 °C to be well in
excess of 30 h.
(8) Fluorescence spectra were obtained according to the procedure
described in ref 5. Monolayers were excited at 400 nm and afforded the
following emission spectra reported as emission wavelength (reaction
solvent): 17b 589 (ethanol), 591 (acetone), 592 (dichloromethane); 18b
571 (ethanol), 566 (acetone), 564 (dichloromethane); 19a, 20a 588 (ethanol),
591 (acetone), 595 (dichloromethane).
(9) Pure octanethiol monolayer and gold substrate showed no adsorption
of aldehyde upon identical treatment.
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Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 28, 1997 6675
Scheme 3
To distinguish between these two possibilities, a second set
of experiments was conducted using fluorescently labeled
thiazole dimer monolayers (18b). These SAMs were treated
with benzaldehyde in the absence of triethylamine. The
resulting SAMs showed fluorescence emissions, albeit at
somewhat diminished intensities, corresponding to the presence
of anthracyl on the surface. Thus, dimer adducts 19b and 20b
appear to be stable under these conditions. Interestingly,
treatment of 18b with excess benzaldehyde in the presence of
triethylamine resulted in almost complete loss of fluorescence
presumably due to the cleavage of dimer and loss of the
fluorescent anthracyl group to afford 17a. It should be noted
that the thiazole dimer monolayer 18b was inert to exposure to
triethylamine in the absence of benzaldehyde. Taken together,
these results suggest that a stable intermediate adduct (i.e., 19/
20) between the thiazole dimer and the aldehyde is formed in
the absence of base and that base and excess aldehyde result in
cleavage of the dimer.
The synthetic transformations 15 f 16 f 18 f 19/20 f 17
model pathway B′′ in Scheme 1 and confirm the role of the
dimer as a competent intermediate on a pathway for the acyloin
condensation. The apparent stability of dimer/aldehyde adducts
19 and 20 in the absence of triethylamine reinforces the
importance of the base in the overall reaction. We believe that
the loss of fluorescence of 19 and 20 is due to base-promoted
cleavage of the aldehyde dimer on the surface.
In conclusion, we have used multistep synthetic modification
of self-assembled monolayers to probe the mechanism of the
thiazolium-promoted acyloin condensation by isolating inter-
mediates of the mechanistic pathway on the surface of the
monolayer. This work shows the potential of SAMs to serve
as models in which to study reaction mechanism and has
provided insights into the thiazolium-catalyzed acyloin reaction.
We have shown that surface-bound thiazole dimers will add to
aldehydes. Cleavage of the dimer is the major pathway through
which these materials promote the condensation. Thus, we
conclude that thiazole dimers participate in catalysis of the
acyloin condensation reaction via pathway B′′ rather than
pathway B′ and that carbanionic intermediate 4 is not part of
the catalytic cycle (Scheme 1). We are currently pursuing the
use of functionalized SAMs both as mechanistic probes and as
chemoselective catalysts.
dimerized thiazolium SAMs (18b). These experiments achieve
two important goals. First, they demonstrate that dimerization
of surface-bound thiazolium salts is possible. Second, they set
the stage for an investigation of the fate of the dimer under
conditions suitable for the acyloin condensation.
To test the viability of the thiazole dimer as a potential catalyst
in the acyloin condensation reaction, the dimer monolayer 18a,
formed from 15 and the benzylthiazolium salt, was subjected
to a second synthetic transformation. This thiazole dimer
monolayer (18a) was immersed in 1.6 mM solutions of
9-anthraldehyde in ethanol, acetone, or dichloromethane and
warmed to ca. 40 °C. For the first set of experiments, no
triethylamine was added to the solutions. After 12 h, the
monolayers were removed from the reaction mixtures and rinsed.
The resulting monolayers showed fluorescence bands similar
to monothiazolium/9-anthraldehyde adduct monolayer (17b).
Lower fluorescence intensities were observed when excess
triethylamine was added to the reaction mixtures. Two possible
scenarios exist to account for the presence of fluorescent
functionality on the monolayer surfaces. First, dimer 18 might
add to the aldehyde to form regioisomeric adduct SAMs 19a
and 20a10 without undergoing further reaction. Alternatively,
cleavage of the adducts would afford 17b directly from 20a
and also regenerate the ylide/carbene 16 from 19a, which would
then be free to react with additional 9-anthraldehyde to generate
the fluorescently labeled SAM 17b.
Acknowledgment. Financial support was provided by The Aca-
demic Senate of University of California, The Office of the Chancellor,
and the National Science Foundation (CHE-9501728). We thank
Professor M. A. Garcia-Garibay for the use of the SPEX Fluorolog
212 fluorometer. We also thank Mr. S. Hegde for providing 3-benzyl-
4-methylthiazolium bromide.
Supporting Information Available: Experimental procedures for
the preparation of compounds 10-14 and monolayers 15-20 including
1H NMR and 13C spectra; procedures for preparation of monolayers;
procedures for fluorescence experiments; contact angle data (7 pages).
See any current masthead page for ordering and Internet access
instructions.
(10) Due to the unsymmetrical nature of the dimer on the surface, two
regioisomeric addition products on the surface are possible. Examination
of molecular models of these SAMs suggests that the plane of the thiazolium
dimer is roughly parallel to the plane of the surface of the monolayer. Thus,
the steric environments of the two nucleophilic carbon atoms of the dimer
are similar.
JA970627Q