A R T I C L E S
Bass et al.
1
Conversion and selectivity were determined via H NMR by taking
aliquots via syringe filter and diluting with CDCl3. Resonances: 5.6
ppm (â-nitro alcohol product), 7.5 ppm (nitrobenzene), 7.72-7.74 ppm
(R,â-unsaturated product), and 10.1 ppm (4-nitrobenzaldehyde).
Knoevenagel Condensation. A typical reaction was conducted using
about 10 mg of catalyst (the amount of catalyst was fixed at 0.01 molar
equivalents of amine relative to 3-nitrobenzaldyde) in 8 mL of an
anhydrous benzene solution of concentration 0.022 M in 3-nitroben-
zaldyde and 0.044 M of malononitrile. To capped catalysts was added
mesoporous silica (Selecto) as a minimally catalytic desiccant in a ratio
that kept the total number of acidic silanols in the reaction constant.
Catalysts were prepared via thermolysis (Supporting Information) in
the reactor vessel (volume was 10 mL) prior to reactant addition and
kept air free under a N2 environment. The reaction was performed at
room temperature (22 °C), and aliquots were taken by syringe and
analyzed by gas chromatography using 1,3,5-trimethoxybenzene as an
internal standard.
material, and a minor band due to neutral imine tautomer. In
general catalysts 5 and 6 after salicylaldehyde treatment, there
is reversal in the order of intensity of these two bands.
Outer-sphere environment effects are further manifested in
carbamate thermolysis, where the acid-base bifunctional mate-
rial lowers the activation barrier by 2.7 kcal/mol while only a
small dielectric effect of 0.5 kcal/mol is observed. Catalysis in
the Michael and Knoevenagel reactions echo the Henry results
with the high dielectric materials being more active than the
nonpolar material 5. In the presence of water, however, only
the acid-base bifunctional material 4 performs well compared
to anhydrous conditions, resulting in an order of magnitude or
higher activity in comparison with 5 and 6 for all catalytic
reactions. This is due to the depressed catalytic rate in the
nonacidic materials for the ion-pair mechanism, as manifested
in changes in the Henry reaction selectivity, likely due to
competitive protonation by water. The remarkably diverse set
of reactions affected by acid-base bifunctional cooperativity
observed in this Article, including the various catalytic probe
reactions, zwitterion formation during salicyladehyde binding,
and immobilized carbamate thermolysis, is testament to the
promiscuity of acid-base distances attainable in heterogeneous
hybrid organic-inorganic catalysts. These data prove the
concept hypothesized in Scheme 1, relating to the silica surface
providing a range of acid-base distances for bifunctional
cooperativity. In contrast, no evidence was observed for
bifunctional cooperativity in homogeneous calixarene models
despite the presence of acidic groups juxtaposed to a pendent
amine. Altogether, our results are significant for understanding
acid-base bifunctional reactivity in heterogeneous organic-
inorganic catalysts, as well as the chemical reactivity of
heterogeneous primary amine catalysts.
Synthesis of NBoc Protected Calixarenes 7 and 8 via Mitsunobu
Reaction. To a mixture of calix[4]arene (0.154 mmol) and NBoc-
alcohol (0.23 mmol) in 5 mL of THF was added triphenyl phosphine
(0.23 mmol). The resulting mixture was cooled to 0 °C, and diethyl-
azodicarboxylate (0.23 mmol) as 40% solution in toluene was added
dropwise. After 10 min of stirring, the resulting yellow-green solution
was allowed to warm to room temperature. After 24 h of stirring at
room temperature, the solution was evaporated to dryness and the
residue was treated with 2 mL of methanol for 20 min followed by
evaporation. Purification via column chromatography yielded the final
products.
5,11,17,23-Tetra-(tert-butyl)-25-[3-(tert-Butoxycarbonylamino)-
propoxy]-calix[4]arene-26,27,28-triol (Nboc7). After separation by
column chromatography (CH2Cl2/methanol ) 1:0.025 v/v, Rf 0.4), white
powder was obtained in 55% yield: 1H NMR (400 MHz) δ 10.24 (s,
1H, OH), 9.67 (s, 2H, OH), 7.13 (s, 2H, ArH), 7.12 (d, 2H, 2.0 Hz,
ArH), 7.10 (s, 2H, ArH), 7.04 (d, 2H, 2.4 Hz, ArH), 5.80 (s, 1H, NH),
4.31, 4.33 (two d, 2H+2H, 13.2 Hz, ArCH2Ar), 4.19 (t, 2H, 6.0 Hz,
OCH2), 3.64 (m, 2H, CH2N), 3.49 (d, 4H, 13.2 Hz, ArCH2Ar), 2.35
(m, 2H, OCH2CH2), 1.52 (s, 9H, OC(CH3)3), 1.27 (s, 9H, C(CH3)3),
1.26 (s, 18H, C(CH3)3), 1.23 (s, 9H, C(CH3)3).
25-[4-(tert-Butoxycarbonylamino)butoxy]-calix[4]arene-26,27,28-
triol (Nboc8). After separation by column chromatography (CH2Cl2/
methanol ) 1:0.02 v/v, Rf 0.6), white powder was obtained in 50%
yield: 1H NMR (400 MHz) δ 9.74 (s, 1H, OH), 9.72 (s, 2H, OH),
7.04, 7.06, 7.10, 7.12 (four d, 2H+2H+2H+2H, 7.6 Hz, ArH-m), 6.91
(t, 1H, 7.6 Hz, ArH-p), 6.72 (t, 1H, 7.6 Hz, ArH-p), 6.71 (t, 2H, 7.6
Hz, ArH-p), 4.85 (s, 1H, NH), 4.31, 4.38 (two d, 2H+2H, 12.8 Hz,
ArCH2Ar), 4.20 (t, 2H, 6.8 Hz, OCH2), 3.50, 3.51 (two d, 2H+2H,
12.8 Hz, ArCH2Ar), 3.40 (m, 2H, CH2N), 2.21 (m, 2H, OCH2CH2),
1.97 (m, 2H, CH2CH2N), 1.57 (s, 9H, OC(CH3)3).
Experimental Section
General. All reagents were purchased from Aldrich at analytical
grade and used as received, unless otherwise noted. 3-Cyanopropyl-
dimethylchlorosilane was distilled prior to use. Dry solvents were
prepared via distillation using standard methods. 1H NMR spectra were
recorded in CDCl3 (293 K) either on a Bruker AV-300 (300 MHz)
instrument or on an AVB-400 (400 MHz) instrument. Single-crystal
diffraction data were collected at the UC Berkeley College of Chemistry
X-ray Crystallographic Facility. All catalytic reactions were conducted
in a well-ventilated fume hood. FAB-MS spectra were recorded using
a o-nitrophenyl octyl ether (NPOE) matrix at the UC Berkeley Mass
Spectrometry Facility.
Deprotection of Nboc-Calixarenes. To a solution of NBoc-protected
calixarenes (0.09 mmol) in 3.0 mL of dry dichloromethane was added
trifluoroacetic acid (0.9 mmol) at 0 °C. The solution was allowed to
warm to room temperature and then stirred an additional 10 h. The
reaction mixture was then hydrolyzed using a saturated NaHCO3
solution. The aqueous solution was extracted with CH2Cl2 and dried
over Na2SO4. After evaporation of solvent, residue was washed with
hexane to give desired calixarene-amines 7 and 8.
5,11,17,23-Tetra-(tert-butyl)-25-[3-aminopropoxy]-calix[4]arene-
26,27,28-triol (7). White powder was obtained in 98% yield: 1H NMR
(400 MHz) δ 9.00 (br s, 3H+2H, OH+NH2), 7.07 (s, 2H, ArH), 7.00
(s, 4H, ArH), 6.97 (s, 2H, ArH), 4.13 (m, 4H+2H, ArCH2Ar+OCH2),
3.51 (m, 2H, OCH2N), 3.35, 3.39 (two d, 13.6 Hz, ArCH2Ar), 2.43
(m, 2H, OCH2CH2), 1.23 (s, 18H, C(CH3)3), 1.20 (s, 9H, C(CH3)3),
1.13 (s, 9H, C(CH3)3). FAB MS m/z 706.6 [M + H+].
Michael Addition. A typical reaction was conducted using about
10 mg of catalyst (the amount of catalyst was fixed at 0.02 molar
equivalents of amine relative to trans-â-nitrostyrene) in 8 mL of an
anhydrous benzene solution of concentration 0.022 M in trans-â-
nitrostyrene and 0.044 M of malononitrile. Catalysts were prepared
via thermolysis (Supporting Information) in the reactor vessel (volume
was 10 mL) prior to addition and kept air free under a N2 environment.
The reaction was performed at room temperature (22 °C), and aliquots
were taken by syringe and analyzed by gas chromatography using 1,3,5-
trimethoxybenzene as an internal standard.
Henry Reaction. Reactions were conducted using approximately
30 mg of catalyst (the amount of catalyst was fixed at 0.01 molar
equivalents of amine relative to 4-nitrobenzaldehyde). Catalysts were
prepared via thermolysis (Supporting Information) in the reactor vessel
(volume was 10 mL) prior to addition and kept air free under a N2
environment. To this vessel was added a solution containing 5 mmol
nitromethane, 0.5 mmol 4-nitrobenzaldehyde, and 0.05 mmol nitroben-
zene as an internal standard. The reaction was performed at 40 °C.
25-[4-Aminobutoxy]-calix[4]arene-26,27,28-triol (8). White pow-
der was obtained in 95% yield: 1H NMR (400 MHz) δ 7.50 (br s,
3H+2H, OH+NH2), 6.94-7.06 (m, 8H, ArH), 6.58-6.83 (m, 4H,
9
3746 J. AM. CHEM. SOC. VOL. 128, NO. 11, 2006