Remarkable high-yielding chemical modification of gold nanoparticles using uncatalyzed click-type i ,3-dipolar cycloaddition chemistry and hyperbaric conditions

Article abstract of DOI:10.1139/V09-138

Azide-terminated alkyl thiolate monolayer-protected gold nanoparticles (1-C,₁₂MPN) with a core size of 1.8 ± 0.2 nm were prepared. 1-C,₁₂MPN was modified in high yields via an uncatalyzed 1,3-dipolar cycloaddition (clicktype reaction) with a variety of terminal acyl alkynes under hyperbaric conditions at 11 000 atm. The resulting 1,2,3-tria- zole modified MPNs (2-C,₁₂MPN) were characterized using ¹H NMR spectroscopy and were verified by comparison of the spectra to those obtained for the products of the model reactions of 1-azidododecane with the same alkynes. TEM analysis showed that the high-pressure conditions did not affect the size of the gold core, suggesting that the only effect is to facilitate the chemical reaction on the particles.

Full text of DOI:10.1139/V09-138

1708
Remarkable high-yielding chemical modification
of gold nanoparticles using uncatalyzed click-type
1,3-dipolar cycloaddition chemistry and
hyperbaric conditions
Hossein Ismaili, Abdolhamid Alizadeh, Kristen E. Snell, and Mark S. Workentin
Abstract: Azide-terminated alkyl thiolate monolayer-protected gold nanoparticles (1-C12MPN) with a core size of
1.8 0.2 nm were prepared. 1-C12MPN was modified in high yields via an uncatalyzed 1,3-dipolar cycloaddition (click-
type reaction) with a variety of terminal acyl–alkynes under hyperbaric conditions at 11 000 atm. The resulting 1,2,3-tria-
1
zole modified MPNs (2-C12MPN) were characterized using H NMR spectroscopy and were verified by comparison of the
spectra to those obtained for the products of the model reactions of 1-azidododecane with the same alkynes. TEM analysis
showed that the high-pressure conditions did not affect the size of the gold core, suggesting that the only effect is to facili-
tate the chemical reaction on the particles.
Key words: nanoparticles, hyperbaric chemistry, 1,3-dipolar cycloaddition, monolayers.
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Resume : On a prepare des nanoparticules d’or protegees par une monocouche d’alkylthiol (1-C12MPN) portant une fonc-
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tion azide en position terminale et dont le diametre principal est egal a 1,8 0,2 nm. Le produit 1-C12MPN a ete modifie
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avec des rendements eleves par le biais d’une cycloaddition 1,3-dipolaire non catalysee (reaction de type par un clic) avec
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une variete d’acyl–alcynes terminales, dans des conditions hyperbariques, a 11,000 atmospheres. Les nanoparticules d’or
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modifiees, protegees par une monocouche d’alkylthiol (2-C12MPN) et portant un cycle 1,2,3-triazole ont ete caracterisees
par spectroscopie RMN du H et ont ete verifiees par comparaison avec les spectres obtenus pour les produits des reactions
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modeles du 1-azidodecane avec les memes alcynes. Une analyse par microscopie electronique a transmission (MET) a per-
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mis de montrer que les conditions de haute pression n’ont pas affecte la taille du diametre principal de l’or suggerant que
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le seul effet est de faciliter la reaction chimique sur les particules.
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Mots-cles : nanoparticules, chimie hyperbarique, cycloaddition 1,3-dipolaire, monocouches.
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[Traduit par la Redaction]
with little or no byproducts under mild conditions. The later
is of key importance for the functionalization of Au-MPN.
While the catalyzed reaction is effective for the modification
of the CdSe and iron oxide nanoparticles, this approach is not
considered as feasible with gold nanoparticles. Gold MPNs
(now simply referred to as MPNs) in the presence of the Cu
catalyst have been suggested to be unstable, and lead to ag-
gregation or decomposition likely due to the reaction of the
Cu catalyst with the gold surface. In another case, Brennan
et al. reported using the Cu-catalyzed route to modifiy azide-
functionalized 12 nm MPNs with alkyne-appended lipases
but a million-fold excess of Cu was required and the yield
was less than 1% conversion.7 More recently, and while this
work was in progress, Astruc and co-workers reported spe-
cific reaction conditions to circumvent the difficulties of the
Cu(I) click reaction on azide-terminated MPNs.13
Williams and co-workers reported a thorough study show-
ing that the Huisgen dipolar cycloaddition reaction can be
used to modify azide-terminated MPNs with a variety of ac-
tivated alkynes without a catalyst.8 However, the yields (ex-
tent of conversion of the azide groups) were extremely low
(13% and less after 60 h in dioxane, depending on the al-
kyne) and could only be marginally improved by altering
the solvent. In a latter study where they reported on the ki-
netics of this reaction on the MPN, they stated that these
Introduction
The Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of
azides to terminal alkynes to produce a triazole ring, the
‘‘click’’ reaction, is a popular and powerful tool in organic
synthesis and combinatorial chemistry.1 This reaction is also
being exploited in material science applications for the mod-
ification of metal and silica surfaces,2 dendrimers,3 and poly-
mers.4 Recently, the reaction was extended to monolayer-
protected CdSe,5 iron oxide,6 and monolayer-protected gold
nanoparticles (MPN).7–12 Because the 1,3-dipolar cycloaddi-
tion reaction of an alkyne and azide is slow, this type of re-
action is typically done in the presence of a Cu(I) catalyst
because it facilitates the rapid, high reaction conversions
Received 28 April 2009. Accepted 9 July 2009. Published on the
NRC Research Press Web site at canjchem.nrc.ca on
21 November 2009.
H. Ismaili, A. Alizadeh,1 K.E. Snell, and M.S. Workentin.2
Department of Chemistry, The University of Western Ontario,
London, ON N6A 5B7.
1Present address: Chemistry Department and Nanoscience and
Nanotechnology Research Center (NNRC), Razi University,
Kermanshah 67149, Iran.
2Corresponding author (e-mail: mworkent@uwo.ca).
Can. J. Chem. 87: 1708–1715 (2009)
doi:10.1139/V09-138
Published by NRC Research Press

Ismaili et al.
1709
yields were slightly underestimated because of the method
used to follow reaction conversion.9 However, the yields
were still relatively low (22%, or 54% in one specific case)
and did not allow the product MPNs to be completely char-
acterized by NMR spectroscopy. Because of the potential of
this type of reaction as a general approach to surface modi-
fication and to allow the introduction of a variety of func-
tionalities from common starting MPNs, an important goal
is to improve the efficiency of this type of reaction on
MPN. To this end, and while this work was in progress,
Sommer and Weck reported on the microwave-assisted cata-
lyzed 1,3-dipolar cycloaddition of azide-terminated MPNs.10
The method proved successful and allowed a large variety of
terminal alkynes to form triazole-functionalized MPN with
near-quantitative yields, but still required very careful con-
trol of the microwave conditions because excess heating of
the MPN lead to nanoparticle decomposition ascribed to par-
ticle aggregation.
General instrumentation
High-pressure reactions were carried out utilizing a LECO
Tempres High-Pressure chemical reactor, which operates at
1
11 000 atm. H and 13C NMR spectra were recorded, as in-
dicated, on either a Varian Inova 600 (1H: 600 MHz, 13C:
150 MHz) or 400 (1H: 400 MHz, 13C: 100 MHz) spectrom-
eters and were referenced to the residual protons in the sol-
vent relative to (CH3)4Si (d (ppm): chloroform-d, 7.26;
dichloromethane-d2, 5.32; or benzene-d6, 7.15). Mass spectra
and exact mass were recorded on a MAT 8200 Finnigan
High resolution Mass Spectrometer. Infrared spectra were
recorded on a Bruker Vector 33 FTIR spectrometer and are
reported in wavenumbers (cm–1). Melting points were meas-
ured using the Electrothermal 9100 melting-point instrument
and are uncorrected. High resolution transmission electron
microscopy (HRTEM) images were collected on a JEOL
2010F HRTEM.
Recently, we reported that the inefficient modification of a
maleimide-modified MPN by the Diels–Alder reaction at am-
bient conditions with a series of dienes was improved remark-
ably using hyperbaric conditions without affecting the particle
core.14 The hyberbaric method for modification of gold MPNs
was more general and was further used to accelerate the
1,3-cycloaddition of a large variety of nitrones to the malei-
mide-modified MPN in quantitative yields.15 In both these
studies, we showed that the reactions carried out on the
MPNs at ambient temperature and pressure were significantly
slower than the corresponding reactions on model compounds
under the same conditions. We attributed this difference in re-
activity to the unique steric effects of the environment at the
interfacial site of reactivity on the MPN. In the present report,
we extend this methodology to study the Huisgen 1,3-dipolar
cycloaddition of azide-terminated MPN to terminal alkynes to
improve the efficiency of this reaction and to expand the
scope of reactions that can be utilized for modification of
nanoparticles using hyperbaric conditions. The Huisgen
1,3-dipolar cycloaddition of azides to terminal alkynes is also
subject to rate acceleration at elevated pressure, although as
far as we are aware, this has only been the subject of one re-
port.16 Specifically, we report herein that azide-terminated,
1.8 nm core size MPNs prepared to be essentially identical to
the original report of Williams and co-workers,8 will react
with activated acyl–alkynes efficiently under high-pressure
conditions at ambient temperature to form the 1,2,3-triazoles
essentially quantitatively in the absence of a Cu catalyst. This
approach eliminates the complications due to the presence of
catalysts or higher temperatures.
Synthetic details
Dodecanethiolate MPN (C12MPN)
Following the procedures of Brust–Shiffrin and Mur-
ray,17,18 hydrogen tetrachloroaurate (III) trihydrate (0.30 g,
0.77 mmol) was dissolved in 28 mL distilled water (re-
sulting in a bright yellow solution) and then mixed with tet-
raoctylammonium bromide (2.30 g, 4.2 mmol) in 70 mL
toluene. The contents were stirred for 30 min at room tem-
perature to facilitate the phase transfer of the hydrogen tetra-
chloroaurate (III) trihydrate into the toluene layer, which
resulted in the organic layer turning to a dark orange colour
and the aqueous layer becoming clear and colourless. After
phase transfer, the aqueous layer was removed and the or-
ganic layer was cooled to 0 8C in ice bath. Dodecanethiol
(0.468 g, 0.57 mL, 2.31 mmol) was added to the solution
via a volumetric pipette and allowed to stir for 10 min. The
addition of dodecanethiol resulted in a colour change from
brownish-orange to clear and colourless. A fresh solution of
sodium borohydride (0.33 g, 8.7 mmol) in 28 mL water was
then added to the rapidly stirring toluene solution over 5 s.
The solution darkened instantly, eventually becoming dark
brown. The mixture was allowed to stir overnight (~18 h)
as it warmed to room temperature, after which time, the
aqueous layer was removed and the toluene layer was
washed with 3 Â 20 mL distilled water and dried over
MgSO4. The toluene layer was then isolated by gravity fil-
tration and evaporated to dryness. The resulting mixture of
C12MPN and tetraoctylammonium bromide was suspended
in 200 mL of 95% ethanol and placed in the freezer over-
night during which time the C12MPN precipitated from solu-
tion. When the MPN had precipitated, the supernatant was
decanted and the precipitate was dissolved in benzene and
concentrated, resulting in the formation of a film in the
round-bottom flask. This film was washed repeatedly with
10 Â 15 mL of 95% ethanol, resulting in pure C12MPN as
Experimental
Commercial solvents and reagents used
The compounds dodecanethiol, hydrogen tetrachloroaurate
(III), tetraoctylammonium bromide, 1,12-dibromododecane,
11-bromo-1-undecene, azobis(isobutyronitrile) (AIBN), 1-
bromododecane, sodium azide, ethynyl magnesium bromide,
1-octyn-3-ol, and ethyl propionate were all purchased from
Aldrich and used as received. Deuterated benzene (C6D6),
deuterated chloroform (CDCl3), and deuterated dichlorome-
thane (CD2Cl2) (Cambridge Isotope Laboratories) were also
used as received.
1
judged by H NMR spectroscopy, which showed no signs
of free dodecanethiol, dodecyldisulfide, or tetraoctylammo-
nium bromide. The resulting C12MPN was dark brown.
Synthesis of bromo-terminated C12MPN
Approximately 200 mg of C12MPN was dissolved in
60 mL of benzene and degassed with nitrogen. 290 mg
Published by NRC Research Press

1710
Can. J. Chem. Vol. 87, 2009
(1.54 mmol) of 11-bromo-1-undecanethiol was added to the
solution and stirred for 2 days at room temperature. The
mixture was then concentrated and the resulting film was
51.7, 32.1, 29.8, 29.77, 29.71, 29.5, 29.4, 29.0, 26.9, 22.9,
14.3. IR (cm–1): 2955, 2924, 2854, 2095, 1467, 1366, 1258.
1
Synthesis of alkynes (4a–4i)
washed with 95% ethanol and dried. The H NMR spectrum
of this MPN is shown in Fig. S1. 1H NMR (600 MHz,
CD2Cl2) d: 3.4, 1.9, 1.8–1.0, 0.9. The integrated areas of
methylene protons alpha to the bromide and terminal methyl
Compounds 1-pyren-1-yl-propyn-1-one (4a), 1-anthracen-
9-yl-propyn-1-one (4c), propynoic acid phenylamide (4h),8
1-ferrocenyl-2-propyn-1-one (4b),21 and 1-(4-nitrophenyl)-2-
propyn-1-one (4e)22 were prepared by their literature
1
group of dodecanethiolate in the H NMR spectra reveals
1
method, and their H NMR spectra are in accord with those
that the ratio of ligands on the bromoundecane-thiolate-
modified C12MPN was 1:1.2, terminal bromide to terminal
methyl.
reported. Compounds 1-phenyl-2-propyn-1-one (4f), 1-(4-bi-
phenyl)-2-propyn-1-one (4d), and 1-octyn-3-one (4i),23 as
well as 1-(2-methylphenyl)-2-propyn-1-one (4g),24 were syn-
thesized by the following procedure (except for 4i where
commercial alcohol was oxidized by magnesium(IV) oxide),
The required 11-bromo-1-undecanethiol was synthesized
by the reported method.19 11-Bromo-1-undecene (1.5 g,
6.43 mmol), AIBN (0.6 g, 3.65 mmol), and thioacetic acid
(3 mL) were dissolved in toluene and refluxed for 2 h. The
reaction mixture was washed with water and then concen-
trated. The crude product was purified by column chroma-
tography (eluting with 5:1 hexanes/ethyl acetate) to
separate. A solution of 11-bromo-1-undecanethioacetate in
dry methanol was cooled in an ice bath, then 3 mL acetyl
chloride was added dropwise, and the solution was stirred
for 6 h at room temperature. The reaction was quenched by
adding water and extracted with CH2Cl2, and then combined
extracts were washed with water. The organic layer was
dried over MgSO4 and evaporated to get the pure product:
1
and their H NMR spectra are in accord with those reported:
5 mmol of the corresponding aldehyde was dissolve in
10 mL of THF and cooled in an ice bath. 10 mL of ethynyl
magnesium bromide (0.5 mol/L in THF) was added drop-
wise in 15 min. The mixture was allowed to stir for 3 h as
it warmed to room temperature, after which time, the reac-
tion was quenched with saturated NH4Cl and extracted with
ether. Organic layer was dried over MgSO4 and then con-
centrated. The crude product was purified by column chro-
matography (eluting with 3:1 hexanes/ethyl acetate).The
corresponding alcohol was dissolved in 10 mL CH2Cl2 and
5.2 g (60 mmol) of magnesium(IV) oxide was added and
the mixture was stirred at room temperature for 1 h. The
oxidized reagent was removed by filtration through Celite,
the organic layer was washed with water (three times), and
the solvent was evaporated.
1
Yellow oil. H NMR (600 MHz, CDCl3) d: 3.40 (t, J = 6.8
Hz, 2H), 2.51 (q, J = 7.3 Hz, 2H), 1.84 (m, 2H), 1.60 (m,
2H), 1.44 –1.27 (m, 15H).
Synthesis of azide-terminated MPN: (1-C12MPN)
1-C12MPN was prepared according to the procedure of
Fleming et al.8 A 60 mL solution of 0.25 mol/L NaN3 in
DMSO was added to the mixture of the bromo-terminated
MPN (prepared as above) in benzene (~200 mg of bromo-
terminated C12MPN in 60 mL of benzene) and the mixture
was stirred for 48 h. After which time, the reaction was
quenched with water and organic layer was separated and
washed with water three times, dried over MgSO4, and
then concentrated. The resulting film was rinsed with
95% ethanol and dried. 1H NMR (600 MHz, CD2Cl2) d:
3.4, 3.25, 1.9, 1.85–1.0, 0.9. The 1H NMR spectrum of
this 1-C12MPN is shown in Fig. 1a. The integrated areas
of the three types of ligands, determined by decomposition
of 10 mg of 1-C12MPN with ~2 mg of iodine, showed
that the ratio of terminal azide/bromide/methyl was
3.5:1:5. Additionally, 1-C12MPN was characterized using
IR spectroscopy and TEM. IR (cm–1): 2959, 2921, 2853,
2096, 1467, 1366, 1282, 1089, 1040, 801. The average
particle size was determined by analysis of TEM images
of numerous samples: 1.8 0.2 nm
General procedures for azide–alkyne
Huisgen 1,3-dipolar cycloaddition reactions
at high-pressure conditions
Preparation of 2-C12MPN
Approximately 10 mg of 1-C12MPN was dissolved in
~2.0 mL of CH2Cl2 then mixed with 15–20 equiv. of the ap-
propriate activated acyl–alkynes (4a–4j). The mixture was
transferred into a brass-clamp-sealed PTFE tube and placed
in the LECO Tempres High-Pressure reactor at 11 000 atm
for 15–24 h. The product 2a–2j-C12MPNs were purified by
washing with 95% ethanol and then CH3CN to remove any
1
unreacted alkyne. IR and H NMR spectroscopy were used
to check the completion of the reaction, as described below,
and purity of the resulting 2a–2j-C12MPNs. The NMR spec-
tra obtained were compared to those of the products of the
model reaction, 5a–5j. These are provided, along with IR
spectra in the Supporting information.
1
2a-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.63–7.73,
4.28, 3.40. IR (cm–1, dropcast on NaCl): 2921, 2851, 1643,
1467, 1225, 923, 849, 805, 716.
Synthesis of 1-azidododecane (3)
1
2b-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.23, 5.49,
A solution of 1-bromododecane (2 g, 8 mmol) and NaN3
(0.57 g, 8.8 mmol) in DMSO (30 mL) was stirred overnight
at room temperature. The reaction mixture was diluted with
diethyl ether and washed with water five times to remove
DMSO. The ethereal layer was dried over MgSO4 and con-
centrated. The spectral data are in accord with the litera-
4.95, 4.63, 4.42, 4.14, 3.66, 3.41, 3.25, 1.9–0.88. IR (cm–1,
dropcast on NaCl): 2925, 2853, 2096, 1631, 1530, 1453,
1260, 1039, 825, 721.
1
2c-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.58, 8.04,
7.73, 7.39, 4.16, 3.40, 1.70–0.86 IR (cm–1, dropcast on
NaCl): 2962, 2921, 2851, 1678, 1467, 1261, 1095, 1019, 805.
1
ture.20 Colourless oil. H NMR (400 MHz, CDCl3) d: 3.25
1
(t, J = 6.9 Hz, 2H), 1.59 (m, 2H), 1.37–1.26 (broad, 18H),
2d-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.45–8.30,
0.88 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) d:
7.67–7.42, 4.41, 3.40, 1.94–0.87. IR (cm–1, dropcast on
Published by NRC Research Press

Ismaili et al.
1711
NaCl): 2961, 2922, 2851, 1652, 1603, 1458, 1261, 1092,
1056, 906, 801, 749.
128.7, 129.1, 131.1, 133.4, 149.0, 192.0. IR (cm–1, dropcast
on NaCl): 3132, 3056, 2920, 2852, 1653, 1525, 1470, 1180,
884, 841, 729. MS (EI): Exact mass (C29H35N3O) calcd.:
441.2780, found: 441.2783.
1
2e-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.58, 8.33,
4.45, 3.40, 1.97–0.87. IR (cm–1, dropcast on NaCl): 2960,
2920, 2851, 1653, 1525, 1343, 1261, 1093, 1041, 848, 798.
5d: Yellow solid, mp 94–98 8C. 1H NMR (600 MHz,
CDCl3) d: 8.55 (d, J = 8.2 Hz, 2H), 8.27 (s, 1H), 7.75 (d, J
= 8.2 Hz, 2H), 7.66 (d, J = 7.4 Hz, 2H), 7.48 (t, 2H), 7.40
(t, J = 7.3 Hz, 1H), 4.45(t, J = 7.2 Hz, 2H), 2.00–1.95 (m,
2H), 1.37–1.25 (broad, 18H), 0.88 (t, J = 6.9 Hz, 3H). 13C
NMR (150 MHz, CDCl3) d: 14.1, 22.6, 26.4, 28.9, 29.2,
29.3, 29.4, 29.5, 30.1, 31.9, 50.8, 127.0, 127.3, 128.1,
128.2, 128.9, 131.2, 135.3, 140.0, 145.8, 148.2, 185.2. IR
(cm–1, dropcast on NaCl): 3126, 2918, 2848, 1633, 1602,
1523, 1467, 1344, 1255, 909, 876, 851, 746, 692. MS (EI):
Exact mass (C27H35N3O) calcd.: 417.2780, found: 417.2787.
5e: Yellow solid, mp 74–76 8C. 1H NMR (400 MHz,
CDCl3) d: 8.64 (d, J = 9.0 Hz, 2H), 8.35 (d, J = 9.0 Hz,
2H), 8.32 (s, 1H), 4.46 (t, J = 7.2 Hz, 2H), 2.01–1.94 (m,
2H), 1.35–1.24 (broad, 18H), 0.86 (t, J = 6.8 Hz, 3H). 13C
NMR (100 MHz, CDCl3) d: 14.0, 22.6, 26.4, 28.9, 29.2,
29.3, 29.4, 29.5, 30.1, 31.8, 50.8, 123.4, 128.5, 131.6,
141.2, 147.4, 150.3, 183.8. IR (cm–1, dropcast on NaCl):
3129, 2915, 2849, 1643, 1599, 1518, 1331, 1237, 1047,
1016, 911, 881, 847, 785, 725, 694. MS (EI): Exact mass
(C21H30N4O3) calcd.: 386.2317; found: 386.2320.
1
2f-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.34, 7.59–
7.46, 4.40, 3.40, 1.90–0.87. IR (cm–1, dropcast on NaCl):
2964, 2924, 2854, 1653, 1603, 1457, 1261, 1115, 1019,
904, 815, 698.
1
2g-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.18, 7.67,
7.38–7.26, 4.36, 3.38, 2.38, 1.89–0.87. IR (cm–1, dropcast
on NaCl): 2918, 2849, 2075, 1657, 1524, 1457, 1228, 1015,
904, 798, 742.
1
2h-C12MPN: H NMR (600 MHz, CD2Cl2) d: 9.09, 8.24,
7.71, 7.33, 7.13, 4.36, 3.41, 1.86–0.87. IR (cm–1, dropcast
on NaCl): 2961, 2921, 2851, 2094, 1678, 1599, 1467, 1260,
1087, 1036, 797.
1
2i-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.18, 4.33,
3.37, 1.87–0.87. IR (cm–1, dropcast on NaCl): 2955, 2921,
2852, 1739, 1437, 1260, 1224, 1199, 1108, 1039, 800, 721.
1
2j-C12MPN: H NMR (600 MHz, CD2Cl2) d: 8.15, 4.39,
3.40, 3.25, 3.06, 1.92–0.89. IR (cm–1, dropcast on NaCl):
2922, 2852, 2091, 1691, 1468, 1261, 1224, 798, 723.
Preparation of 5a–5j
5f: Yellow solid, mp 49–51 8C. 1H NMR (400 MHz,
CDCl3) d: 8.43 (d, J = 8.7 Hz, 2H), 8.25(s, 1H), 7.61 (t,
1H), 7.51 (t, 2H), 4.44 (t, J = 7.2 Hz, 2H), 1.99–1.92 (m,
2H), 1.34–1.24 (broad, 18H), 0.86 (t, J = 6.8 Hz, 3H). 13C
NMR (100 MHz, CDCl3) d: 14.0, 22.6, 26.4, 28.9, 29.2,
29.3, 29.4, 29.5, 30.1, 31.8, 50.6, 128.1, 128.4, 130.6,
133.2, 136.5, 148.0, 185.7. IR (cm–1, dropcast on NaCl):
3137, 2957, 2853, 1653, 1577, 1260, 1234, 1181, 1045,
1018, 904, 798, 725, 696. MS (EI): Exact mass
(C21H31N3O) calcd.: 341.2467; found: 341.2477.
Alkynes (4a– 4j) (0.15 mmol) and 1-azidododecane (3)
(0.16 mmol) were dissolved in ~2 mL of CH2Cl2 then trans-
ferred into a brass-clamp-sealed PTFE tube and placed in
the LECO Tempres High-Pressure reactor at 11 000 atm and
room temperature for 10 h. The product was removed from
unreacted alkyne by preparative TLC plate (3:1 hexanes/
ethyl acetate). The resulting products, 5a–5j, were character-
ized as summarized below.
5a: Yellow solid, mp 81–84 8C. 1H NMR (600 MHz,
CDCl3) d: 8.61 (d, J = 9.3 Hz, 1H), 8.32–8.30 (m, 2H),
8.25–8.20 (m, 4H), 8.15–8.10 (m, 2H), 7.81 (s, 1H), 4.93 (t,
J = 7.4 Hz, 2H), 2.10–2.04 (m, 2H), 1.49–1.37 (m, 4H),
1.32–1.25 (broad, 14 H), 0.87 (t, J = 7.0, 3H). 13C NMR
(CDCl3) d: 14.1, 22.7, 26.6, 29.1, 29.3, 29.4, 29.5, 29.6,
30.5, 31.9, 50.9, 123.8, 123.9, 124.1, 124.8, 126.5, 126.6,
126.7, 126.9, 127.1, 127.2, 127.3, 130.0, 130.2, 130.9,
131.1, 132.1, 134.3, 140.4, 186.0. IR (cm–1, dropcast on
NaCl): 3240, 2923, 2853, 1650, 1510, 1221, 999, 926, 849,
708. MS (EI): Exact mass (C31H35N3O) calcd.: 465.2780,
found: 465.2777.
1
5g: Yellow oil. H NMR (400 MHz, CDCl3) d: 8.15 (s,
1H), 7.77 (d, J = 7.7 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H),
7.31–7.28 (m, 2H), 4.42 (t, J = 7.2 Hz, 2H), 2.45(s, 3H),
1.98–1.91 (m, 2H), 1.33–1.25 (broad, 18H), 0.87 (t, J = 6.8
Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 14.1, 20.3, 22.6,
26.4, 28.9, 29.2, 29.3, 29.4, 29.5, 30.1, 31.8, 50.6, 125.2,
127.5, 130.1, 131.2, 131.3, 137.1, 137.9, 148.3, 189.5. IR
(cm–1, dropcast on NaCl): 3135, 2925, 2855, 1658, 1524,
1460, 1440, 1233, 1042, 905, 742 MS (EI): Exact mass
(C22H33N3O) calcd.: 355.2623, found: 355.2614.
1
1
5h: Yellow solid, mp 128–130 8C. H NMR (400 MHz,
5b: Maroon oil. H NMR (400 MHz, CDCl3) d: 8.16 (s,
CDCl3) d: 8.94 (s, 1H), 8.13 (s, 1H), 7.69 (J = 7.6 Hz, 2H),
7.38 (t, 2H), 7.15 (t, J = 7.4 Hz, 1H), 4.42 (t, J = 7.2 Hz,
2H), 1.98–1.92 (m, 2H), 1.33–1.25 (broad, 18H), 0.87 (t, J
= 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 14.1, 22.7,
26.4, 28.9, 29.3, 29.34, 29.5, 29.6, 30.1, 31.9, 50.9, 119.8,
124.5, 125.5, 129.1, 137.5, 143.4, 163.9. IR (cm–1, dropcast
on NaCl): 3317, 3139, 2920, 2851, 1664, 1558, 1437, 1047,
800, 749, 689. MS (EI): Exact mass (C21H32N4O) calcd.:
356.2576, found: 356.2589.
1H), 5.52–5.51 (m, 2H), 4.65–4.64 (m, 2H), 4.42 (t, J = 7.2
Hz, 2H), 4.17 (s, 5H), 2.00–1.93 (m, 2H), 1.35–1.25 (broad,
18H), 0.87 (t, J = 6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d: 14.1, 22.7, 26.4, 28.9, 29.3, 29.4, 29.5, 29.6, 30.1, 31.9,
50.5, 70.2, 71.6, 73.0, 126.3, 149.1, 189.2. IR (cm–1, drop-
cast on NaCl): 3117, 2925, 2853, 1629, 1528, 1444, 1377,
1260, 1107, 1041, 826, 771. MS (EI): Exact mass
(C25H35N3FeO) calcd.: 449.2129, found: 449.2139.
5c: Yellow solid, mp 84–86 8C. 1H NMR (600 MHz,
CDCl3) d: 8.57 (s, 1H), 8.05 (d, J = 8.2 Hz, 2H), 7.97 (s,
1H), 7.80 (d, J = 8.6 Hz, 2H), 7.47 (t, 2H), 7.42 (t, 2H),
4.35(t, J = 7.3 Hz, 2H), 1.92–1.87 (m, 2H), 1.31–1.24
(broad, 18H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (150
MHz, CDCl3) d: 14.1, 22.7, 26.4, 28.9, 29.3, 29.4, 29.5,
29.6, 30.1, 31.9, 50.7, 125.0, 125.4.3, 126.6, 127.4, 128.5,
1
5i: Colourless solid, mp 80–82 8C. H NMR (400 MHz,
CDCl3) d: 8.02 (s, 1H), 4.39 (t, J = 7.2 Hz, 2H), 3.11 (t, J
= 7.5 Hz, 2H), 1.95–1.88 (m, 2H), 1.78–1.71 (m 2H), 1.40–
1.24(broad, 22H), 0.92–0.86 (m, 6H). 13C NMR (100 MHz,
CDCl3) d: 13.9, 14.1 22.5, 22.7, 23.7, 26.4, 28.9, 29.31,
29.33, 29.5, 29.6, 30.1, 31.5, 31.9, 39.5, 50.6, 125.1, 148.1,
Published by NRC Research Press

1712
Can. J. Chem. Vol. 87, 2009
1
195.7. IR (cm–1, dropcast on NaCl): 3102, 2915, 2847, 1687,
1469, 1241, 1159, 1055, 970, 887, 719. MS (EI): Exact mass
(C20H37N3O) calcd.: 335.2936, found: 335.3001.
Fig. 1. H NMR spectra of 1-C12MPN (a) and representative product
1,2,3-triazoles 2-C12MPN formed in click reactions of 1-C12MPN
with acyl alkynes 4h, 4d, and 4c: (b) 2h-C12MPN, (c) 2d-C12MPN,
and (d) 2c-C12MPN. Solvent: CD2Cl2, residual proton signal is indi-
cated by *.
1
5j: Colourless oil. H NMR (400 MHz, CDCl3) d: 8.11 (s,
1H), 4.70 (t, J = 7.4 Hz, 2H), 4.38 (q, J = 7.1 Hz, 2H),
1.94–1.84 (m, 2H), 1.39 (t, J = 7.1 Hz, 2H), 1.31–1.24
(broad, 18H), 0.87 (t, J = 6.5 Hz, 3H). 13C NMR (100
MHz, CDCl3) d: 14.1, 14. 14, 22.7, 26.4, 29.0, 29.3, 29.4,
29.5, 29.6, 30.3, 31.9, 50.4, 61.7, 127.7, 137.9, 158.5. IR
(cm–1, dropcast on NaCl): 2956, 2855, 1731, 1528, 1457,
1311, 1255, 1092, 772. MS (EI): Exact mass (C17H32N3O2)
(M+H+) calcd.: 310.2494, found: 310.2482.
Results and discussion
The azide-terminated MPNs were prepared according to
the method recently reported.8 Starting with 1.8
0.2 nm
dodecanethiol-stabilized MPN (C12-MPN), 11-bromoundeca-
nethiol was introduced onto the MPN using the place-ex-
change method to yield a mixed monolayer containing Br-
terminated undecanethiol ligands. Reaction of this MPN
with NaN3 in DMSO introduced the azide functionality onto
the MPN. The ratio of terminal azide/bromide/methyl in the
newly made mixed MPN was estimated to be roughly
1
3.5:1:5 by H NMR spectroscopy of I2-reduced MPNs. This
mixed monolayer particle (1-C12MPN) was further character-
and 4i (Table 1). Presumably, extending the reaction times
further would lead to more complete conversion for these
two less activated alkynes.
ized by IR and UV–vis spectroscopy and TEM. Figure 1a
1
shows the H NMR spectrum of 1-C12MPN. The key diag-
nostic signals are the characteristically broad signals due to
the methylene protons alpha to the azide and bromide func-
tionality at 3.24 and 3.41 ppm, respectively. The IR spectrum
of 1-C12-MPN also shows a strong absorbance at 2096 cm–1
due to the antisymmetric –N=N=N stretch in addition to the
CH2/CH3 stretches at 2959, 2921, and 2852 cm–1.
After completion of the reaction and removal of the reac-
tion mixture from the high-pressure reactor, the mixtures
were washed several times to remove excess alkyne from the
MPN and a H NMR spectrum was recorded. These spectra
show that 1-C12MPN had reacted to form the corresponding
1
1,2,3-triazole product 2-C12MPN. Figures 1b–1d show repre-
1
sentative H NMR spectra of the product 2-C12MPN formed
Compound 1-C12MPN (~10 mg) was then mixed with
each of the activated acyl–alkynes 4a– 4j, shown in
Scheme 1, in a ratio of 1:15–20 in 2 mL of CH2Cl2 and
placed in a high-pressure reactor at 11 000 atm at ambient
temperature. Model reactions of 1-azidododecane (3) with
each alkyne were also performed under high-pressure condi-
tions to aid in monitoring the extent of reaction and to pro-
vide analogous 1,2,3-triazole products (5a–5j) to allow for
characterization of the reactions on 1-C12MPN (Scheme 2).
by reaction of 1-C12MPN with alkynes 4h, 4d, and 4c, re-
spectively. Evidence for the reaction includes the downfield
chemical shift of the protons alpha to the nitrogen atom
from 3.24 ppm in the azide (labeled b) to ~4.2 ppm (labeled
b’), alpha to the triazole ring (Fig. 1). The disappearance of
the signal at 3.24 ppm on the 1-C12MPNs was considered as
a sign of complete conversion of the azide. IR spectra of
2a–2j-C12MPN also show loss of the –N=N=N stretch at
2096 cm–1, verifying completion of the reaction, and a
new stretch at ~ 1639–1670 cm–1 due to the C=O (1734 cm–1
for ester 2j-C12MPN). Common to all spectra is the absence
of the signal at 3.24 due to the CH2 alpha to the azide, and a
new signal appears between 7.8–8.6 ppm (chemical shift
varies slightly with structure) due to the triazole C–H pro-
ton (labeled c in the spectra). Of course, other signals in
the NMR spectra due to the functionality introduced with
the cycloaddition with the alkyne are assignable easily by
comparison to the spectra of the products of the model reac-
tions, 5a–5j. These are provided in the Supporting informa-
tion. For example, The 1H NMR spectra of 2h-C12MPNs
(Fig. 1b) shows new peaks in the aromatic region attrib-
uted to the aromatic ring as well as the triazole C–H pro-
ton at 8.25 ppm and the amide proton at 9.15 ppm,
verifying the formation of the triazole ring. It is noticeable
1
The extent of reaction of 1-C12MPN was followed by H
NMR and IR spectroscopy. The reaction was considered
complete when there was no evidence of the protons alpha
1
to the azide in the H NMR spectrum and by the disappear-
ance of the azide peak in the IR spectrum. For most cases,
this occurred after 15–24 h, depending on the alkyne
(Table 1). We note that high temperatures cannot be em-
ployed to decrease reaction times for 1-C12MPN because
MPNs are not thermally stable for extended periods. The re-
action of 1-C12MPNs with alkynes 4a, 4c, 4d, 4e, and 4f, re-
sulting in the corresponding 2-C12MPNs, was quantitative
after 15 h (perhaps less). Alkynes 4b, 4g, 4h, 4i, and 4j had
slightly lower 1,3-dipolar cycloaddition reactivity, and their
reactions with 1-C12MPNs was carried out for 24 h. After
which time, the azide peak in the IR spectra was completely
absent for mixtures containing 4g, 4h, and 4j, indicating
near-complete conversion, but only around 80% conversion
was observed for the reaction of the 1-C12MPNs with 4b
1
that the H NMR of the 2a- and 2c-C12MPN with a rela-
tively bulky R group (pyrene and anthracene) shows broad-
Published by NRC Research Press

Ismaili et al.
1713
Scheme 1. The 1,3-dipolar cycloaddition of 1-C12MPN with a variety of terminal acyl-alkynes (4a– 4j) at 11 000 atm.
Scheme 2. Model reaction of 1-azidododecane (3) with alkenes (4a– 4j) to yield 1,2,3-triazoles (5a–5j).
Table 1. Extent of reaction of 1-C12MPN with alkynes
(4a– 4j) via uncatalyzed 1,3-dipolar cycloaddition reaction
at atmospheric and hyperbaric pressure conditions.
tion. Although these reactions were only carried out at rel-
atively small scale, they are easily scalable to the gram
scale (or more) making the use of the hyperbaric reactor
practical for synthetic preparations on MPNs. As men-
tioned above, to facilitate the assignment of the protons of
the 1H NMR spectra of 2-C12MPNs, the reactions were
also carried out using the solution-phase reaction of 1-azi-
dododecane with the same alkynes at high-pressure condi-
tions as a model reaction to yield compounds 5a–5j
(Scheme 2). Compounds 5a–5j could be characterized
% Conversion
% Conversion
(11 000 atm)
Alkyne
4a
4b
4c
4d
4e
4f
4g
4h
4i
(atmospheric pressure)a
13
12
6
6
6
NRb
NR
NR
NR
NR
>95c
>80d
>95c
>95c
>95c
>95c
>95d
>95d
>80d
>95d
1
more completely via H NMR, 13C NMR, and IR spectro-
scopy, as well as mass spectrometry (see Experimental).
1
Because the H NMR spectra of 5a–5j are not as broad as
those of 2-C12MPN, they are more easily assignable, and
hence they provide the confidence in the assignments of
the spectra for 2-C12MPN. For example, Fig. 2 shows the
1H NMR spectra of 2g-C12MPN and the model compound
5g, respectively. The signals at 4.4 ppm (b’), alpha to the
triazole ring, and 8.18 ppm (c), attributed to the C–H pro-
ton of triazole ring, verify the formation of the cycloaddi-
tion product on the MPN. The other signals observed for
2g-C12MPN are also readily assignable because the inten-
sity and chemical shift are comparable to 5g except the ex-
pected broadening of the 1H NMR signals on the MPN.
The labeled 1H NMR spectra of 2a–2j-C12MPN and the
corresponding model compounds 5a–5j are provided in the
Supporting information. In general, the reaction of the 1-
azidododecane with the less-electron-deficient dipolaro-
philes (4d, 4f, and 4h) provided a higher yield in the
same reaction time compared with the more-electron-
deficient (4e and 4j) and the sterically hindered (4a– 4c)
4j
a60 h in dioxane; see ref. 8.
bNR: Not reported.
cAs determined by NMR after 15 h.
dAs determined by NMR after 24 h.
ened peaks, especially for the peak assigned to the methyl-
ene group (b’) adjacent to the triazole ring, in comparison
with the 2-C12MPNs with less-bulky R groups. This broad-
ness suggests that the bulky group limits the mobility of
these groups on the MPNs more than that of the less-bulky
R groups. UV–vis spectra and TEM of the particles after
reaction verify that there is no measureable change to the
Au core size and that the only effect of the high-pressure
conditions is the acceleration of the 1,3-dipolar cycloaddi-
Published by NRC Research Press

1714
Can. J. Chem. Vol. 87, 2009
1
Fig. 2. H NMR spectra of (a) 2g-C12MPN in CD2Cl2* and (b) compound 5g in CDCl3.
alkynes; a result mirrored in the reactivity of 1-C12MPN
with the same alkynes (Table 1).
Supplementary data
Supplementary data (1H NMR spectra of the bromine-
The Huisgen uncatalyzed 1,3-dipolar cycloaddition of an
azide with an alkyne can lead to two possible regioisomers:
the 1,4- (anti) and 1,5- (syn) isomers. Only the 1,4 isomer is
shown as a product in Schemes 1 and 2. In cases where the
alkyne is electron-defficient25 or when a sterically bulky
azide26 is used, the 1,4-isomer is usually the major product
(e.g., 1,3-dipolar cycloadditions of 1-azidoadamantane with
ethyl propionates form only 1,4 isomers). The formation
and ratio of the 1,4- and 1,5-isomers can be determined by
1H NMR spectroscopy because the C–H triazole protons of
the 1,4- and1,5-isomers are different, the latter usually
terminated-MPN, 1-C12MPN, 1H NMR and IR spectra
1
2a–2j-C12MPN, and H NMR spectra of 5a–5j) for this ar-
ticle are available on the journal Web site (canjchem.nrc.ca)
or may be purchased from the Depository of Unpublished
Data, Document Delivery, CISTI, National Research Coun-
cil Canada, Ottawa, ON K1A 0R6, Canada. DUD 5301. For
more information on obtaining material, refer to cisti-icist.
nrc-cnrc.gc.ca/cms/unpub_e.shtml.
Acknowledgements
1
downfield of the former. In this study, the H NMR spectra
This work was supported by the Natural Sciences and En-
gineering Research Council of Canada (NSERC Discovery
and RTI for the hyberbaric reactor). Doug Hairsine is
thanked for technical assistance with mass spectrometry
measurements. M. A. Kerr is thanked for use of the high-
pressure apparatus.
of 2a–2j-C12MPNs show only one peak that can be assigned
as a C–H proton of the triazole ring; this indicates that there
is one major isomer formed. Because the alkynes used in
this study are electron-deficient and the environment around
the azide moiety in 1-C12MPN is sterically hindered, the for-
mation of 1,4-isomer is the regioisomer that is most likely
preferred.
References
The NMR and IR data together indicate the essentially
quantitative conversion of the azide-terminated ligand
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