Synthesis of bridged molecular gyroscopes with closed topologies: Triple one-pot macrocyclization

Article abstract of DOI:10.1021/jo201513y

We describe the synthesis and characterization of six bridged molecular gyroscopes with m-alkoxy-substituted trityl stators and dialkynylphenylene rotators. All of the bridged molecular gyroscopes were synthesized convergently to form the phenolic stator-

Full text of DOI:10.1021/jo201513y

ARTICLE
pubs.acs.org/joc
Synthesis of Bridged Molecular Gyroscopes with Closed Topologies:
Triple One-Pot Macrocyclization
Patrick Commins, Jose E. Nu~nez,† and Miguel A. Garcia-Garibay*
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States
S Supporting Information
b
ABSTRACT: We describe the synthesis and characterization of
six bridged molecular gyroscopes with m-alkoxy-substituted
trityl stators and dialkynylphenylene rotators. All of the bridged
molecular gyroscopes were synthesized convergently to form
the phenolic statorꢀrotator framework, while the alkyl and
benzophenone bridges were installed in one step by relatively
efficient one-pot reactions to form macrocyclic diether or
diester linkages. The isolated yield per bond-forming reaction
varied from ca. 42% to 80%, with one exception where macro-
cyclization failed to produce the desired product. The molecular
structure and crystal packing of each of the bridged molecular gyroscopes were determined via single crystal X-ray diffraction. Like
most molecular gyroscopes with open topologies previously studied, the singly bridged structures pack by interdigitating one trityl
stator in one molecule next to the rotator of an adjacent molecule in the lattice. In contrast, the triply bridged molecular gyroscopes
were found to pack in lamellar sheets that prevent the rotatorꢀstator interdigitation of adjacent molecules. However, solvent
molecules and conformationally flexible bridges tend to fill in the packing volume by collapsing next to the rotator or by extending
one of their bridges into the cavity of a neighboring molecule.
’ INTRODUCTION
gigahertz (1012 sꢀ1 2a,13 regime. Not surprisingly, we have found
)
that these structures have a tendency for adjacent molecules to
interdigitate and solvent molecules to pack close to the rotator
(Figure 2A), making a strong case for the development of
methods for the synthesis of triply bridged structures with closed
topologies (Figure 2B).
The field of artificial molecular machines has been the subject
of intense interest for the past 30 years.1 Recent interest in the
development of functional materials has led to the exploration of
amphidynamic crystals built with a combination of rigid compo-
nents and moving parts.2ꢀ4 It has been suggested that amphi-
dynamic crystals will have physical properties that are a function
of their internal dynamics and will provide opportunities for the
development of new types of functional materials.2,5 One of the
simplest and most promising strategies involves the preparation
of molecular rotors6 with structures that emulate the architecture
and dynamics of macroscopic gyroscopes, which we2,7 and
others8,9 have addressed from synthetic and functional perspec-
tives. Gyroscopes possess a rotating mass linked by an axle to a
shielding structure that provides a frame of reference and acts as
the stator to help describe the internal motion (Figure 1). At the
molecular level, we have pursued these features with axially
linked rotators such as a p-phenylene2,7 and more symmetric
groups,10 two triple bonds acting as the rotary axle, and two bulky
triarylmethyl groups serving as the stator (Figure 1b).
It is well-known that rotation of groups linked to triple bonds
is essentially barrierless in the gas phase,11 and we have shown
that rotation in the solid state is determined by the hindrance
imposed by close neighbors and solvent molecules packing in the
vicinity of the rotator.12 We have shown that molecular gyro-
scopes with open topologies create low-density regions in the
center of their structures, and that they are able to support
rotational dynamics that range from a few hertz up to the
As illustrated in Figure 2B, molecular gyroscopes with closed
topologies require structures with longitudinal bridges that span
from the top to the bottom of the structure to shield the rotator
from contacts with the environment. Our first efforts on the
synthesis of triply bridged molecular gyroscopes by direct
macrocyclization with simple alkyl chains met with problems
due to the formation of one “meridional” and two “zonal” bridges
(Scheme 1, compound 4).14 We discovered that all-axial bridged
structures with 8- and 10-carbon alkanediyl chains were not
formed by reaction of 3 equiv of the corresponding α,ω-
dibromoalkanes with hexaphenol 1, or by ring-closing metathesis
of the hexaalkenyl ethers 2, a procedure that had been success-
fully used by Gladyzs and co-workers with metal-coordinated
triarylphosphines.7 The synthesis of compound 3 required a
stepwise, directed macrocyclization with a nonsymmetric pre-
cursor (5) bearing the alkyl chains and the phenols on trityl
groups at opposite ends.13
A qualitative analysis of molecular models indicates that zonal
bridges are probably formed because the chain conformations
Received: August 1, 2011
Published: September 13, 2011
r
2011 American Chemical Society
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required for side-to-side cyclization are more easily attained than
those required for the meridional bridges. In fact, while the
distance between zonal phenols ranges from ca. 6.5 to 8.5 Å, the
distances between meridional phenols span from 10.5 to 12.5 Å,
suggesting that meridional alkyl bridges require entropically
more demanding extended conformations. On the basis of this
analysis, it should be possible to avoid zonal bridging by using
rigid bridges with end-to-end distances that are longer than ca.
8.5 Å. In order to test this hypothesis, we decided to explore the
use of 4,40-dibromomethyl benzophenone and 4,40-benzophe-
none dicarboxylic acid dichloride as bridging groups. While the
relatively long distance between the reactive 4,40-carbon atoms
(ca. 10 Å) in the substituted benzophenones is not expected to
lead to zonal bridges, we envisioned the stereoelectronic de-
mands of the corresponding tetragonal and trigonal cyclization
reactions to be different and worth exploring. To evaluate the
efficiency of the macrocyclization reaction with ether and ester
bridges, we decided to analyze the formation of the singly bridged
structures 6 and 9 with 10-carbon chains starting from the
diphenol 17. With good results in both of those reactions, we
next confirmed the formation of the benzophenone mono-
bridged structures 7 and 8, both of which were found to proceed
in reasonable yields. A series of four singly bridged molecular
gyroscopes and three triply bridged ones were synthesized
(Figure 3), and their packing motifs were analyzed by single
crystal X-ray diffraction. Compound 12 is not a bridged gyro-
scope but was obtained during the synthesis of 8 in significant
yields. The formation of dimer 12 indicates that the synthesis of
11 would be unlikely, as each bridge could dimerize and prevent a
fully intramolecularly cyclized product. The synthesis of a triply
bridged ester linked alkyl rotor analogous to 11 was not
performed using this method, as there would be competing
regioselectivity between the meridional and zonal bridges, as
shown in the one-step synthesis of 3.14
Figure 1. (a) A macroscopic toy gyroscope is assembled with a rotating
mass (rotator) that is linked to a stator made by two circles that enclose
the rotator. (b) A molecular gyroscope with an open topology consists of
a phenylene rotator (red) and two trityl stators in blue, and (c) a
molecular gyroscope with a closed topology consists of a phenylene
rotator, two trityl stators, and three benzophenone bridges.
’ RESULTS AND DISCUSSION
Synthesis and Characterization. The synthesis of diphenol
17, which is the common intermediate for compounds 6, 7, 8, 9,
and 12, was completed by a straightforward four-step synthesis
(Scheme 2). The mono-m-methoxy trityl alcohol 14 was synthe-
sized by lithiation of 3-bromoanisole using n-butyllithium, which
Figure 2. (A) Nonbridged molecular gyroscopes have a tendency to
interdigitate one molecule’s trityl stator into another molecule’s pheny-
lene rotator. (B) Bridged molecular gyroscopes are unable to inter-
digitate a trityl stator into the adjacent molecules’ rotator. Rotators are
shown in red, stators in blue, and bridges in green.
Scheme 1
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Figure 3. The eight bridged molecular gyroscopes synthesized via a one-pot reaction.
Scheme 2
was followed by reaction with benzophenone. The resulting
alcohol was converted to the mono-m-methoxy trityl chloride by
refluxing in acetyl chloride, which was subsequently refluxed in
ethynylmagnesium bromide to generate the mono-m-methoxy
trityl alkyne 15. This compound was converted to the di-m-
methoxy derivative 16 using diiodobenzene and standard Sono-
gashira conditions. Compound 16 was demethylated using BBr3
to afford diphenol 17 in an overall yield of 47%.
solutions of 1 or 17 and the α,ω-dihalo-substituted bridge
precursor are slowly added over 8 h into a solution of DMF
containing K2CO3 as a mild base. The slow and concomitant
addition of the phenol and bridge precursor into the reaction
helps maintain a high dilution, which promotes the intramole-
cular cyclization and prevents oligomerization. The resulting
molecular gyroscopes were purified using column chromatogra-
phy and characterized by 13C NMR, 1H NMR, attenuated total
reflectance (ATR) FTIR, high resolution MALDI-TOF mass
spectrometry, and single crystal X-ray analysis. Compounds 3,
6ꢀ10, and 12 were isolated in moderate yields as detailed in
Table 1.
The synthesis of 1 has been previously described15 following a
reaction sequence similar to that used for the preparation of 17
with the exception that diethyl carbonate instead of benzophe-
none is used to react with the lithium reagent obtained from
3-bromoanisole in the first reaction. The synthesis affords the
hexa-m-phenol gyroscope 1 in four steps with an overall yield of
54%. The general one-step synthesis of the bridged compounds
6ꢀ10 and 12 is illustrated in Scheme 3. Freshly prepared
Comparing the yields per bond formed for a singly bridged
gyroscope (e.g., compounds 6 and 7 with two bonds each) to its
corresponding triply bridged analogue (compounds 3 and 10
with six bonds each) demonstrates that they are similar. Although
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this analysis is based only on two examples, this indicates that the
addition of the final bridging group was as probable as the
addition of the first. One can see from the table that the yields of
bridging using ether linkages tend to be higher (67ꢀ80%) than
those obtained using esters (42ꢀ45%). In fact, the low yield for
compound 8 correlates with the formation of product 12, which
is a 58-membered macrocycle.16 That dimerization is favored
over intramolecular cyclization, which is shown by the increased
yields per bond formed, 42% for 8 vs 68% for 12. The “dimer” 12
was observed when DMAP was used as a base to synthesize 8, as
potassium carbonate only afforded minor amounts of product.
The use of models shows that the phenol has a poor angle of
attack on the activated acylpyridinium monolinked intermediate,
such that the inefficient intramolecular cyclization causes the
intermediate to accumulate and dimerize and form the larger
macrocycle. We speculate that the ether-forming compounds do
not have a poor angle of attack on the monolinked intermediate
and are able to cyclize efficiently. Comparing the results from
the reactions leading to 7 and 8 indicates that trigonal cyclizations
are unfavorable when bridging the gyroscope as compared to the
tetragonal cyclization reactions. The synthesis of compound 11
was attempted, but none of the desired product was detected.
However, considering the low yield per bond of 8 and dimeriza-
tion product for compound 12, it seems unlikely that compound
11 could be made using this method. No dimerizations or
oligomeric products could be isolated from the attempted
syntheses of 11.
phenylene along with those of the unsubsituted phenyl groups in
the case of 7, 8, 9, and 12. With reference to the numbering
shown in Scheme 3, the m-alkoxy-substituted aryl rings are
characterized by an apparent triplet assigned to H10, a doublet
of doublets assigned to H7 and two doublet of doublets of
doublets assigned to H9 and H11 in the range of 6.29ꢀ7.58 ppm.
1
The H NMR also showed a singlet corresponding to the four
protons (H2) in the central phenylenes between 6.86 and 7.44
ppm, indicating a high degree of average symmetry in all the
molecules. The H7 proton for compounds 3, 6ꢀ10, and 12 is
significantly deshielded with a chemical shift at 7.23ꢀ7.84 ppm,
which is 0.45ꢀ1.06 ppm higher than that in the m-phenol
precursors. The increased shielding is due to its forced proximity
above the alkynyl axles as indicated in the crystal structures. The
13C NMR spectra of compounds 3, 6ꢀ10, and 12 shows a single
quaternary trityl carbon (C5, Scheme 3) at 56.0ꢀ56.3 ppm
and only two alkyne signals at 84.7ꢀ85.2 (C3) and 95.9ꢀ97.4
(C4) ppm, further indicating a high degree of symmetry in the
structure.
1
The H NMR spectrum of compound 6, with a single alkyl
bridge, has a multiplet from 7.20 to 7.35 ppm attributed to the 20
phenyl protons in its trityl stators. There is a multiplet at
1.20ꢀ1.80 ppm assigned to the 16 internal hydrogens of the
10-carbon chain as well as a triplet at 3.90 ppm assigned to the
methylene group adjacent to the ether oxygen. There are 12
aromatic carbons in the 13C NMR as well as the quaternary and
alkynyl carbons as previously mentioned. There are 4 alkyl
carbons between 25 and 31 ppm that are assigned to the bridge,
and one signal at 67 ppm corresponding to the carbon adjacent to
the oxygen. The 1H NMR spectrum of the triply bridged
molecular gyroscope 3 is similar to that of 6, with the exception
that the molecule is now D3h symmetric with a simpler appear-
ance in the aromatic region. In analogy to 6, compound 7 has 20
aryl protons from 7.20 to 7.30 ppm, two doublet of doublets of
doublets with J = 8.2, 2.5, 0.9, and J = 7.8, 1.8, 0.9 Hz at 6.96 and
6.34 ppm, respectively, that integrate for 2H, and a singlet at 5.23
ppm for 4H. The latter are assigned to the benzophenone bridge
and the methylene protons, respectively. A 13C NMR signal at
195 ppm corresponds to the carbonyl group of the benzophe-
none bridge, which can be fully accounted for with four aromatic
signals from 131 to 120 ppm and a methylene ether signal at
68 ppm. The 1H and 13C NMR spectra of tribridged compound
10 are similar to those of 7, and similar assignments could be
made for compounds 8 and 12. However, the correct structure
for the latter was suggested from its ESI mass spectrum with a
strong signal at m/z = 1753.583 (2M + H) and by a 2D diffusion
ordered correlation spectroscopy (2D DOSY) comparison of
Compounds 3, 6ꢀ10, and 12 dissolve well in chloroform,
methylene chloride, and toluene and are insoluble in polar
solvents such as acetonitrile and methanol. The 1H NMR spectra
for all of the bridged molecular gyroscopes show the typical motif
of the m-alkoxy-substituted aryl ring and the signals of the central
Scheme 3
Table 1. Yields from Synthesis of Singly and Triply Bridged Molecular Gyroscopes
isolated
isolated yield per bonds
formed (%)
compound
bridge precursor
yield (%)
3
a
27
46
57
18
20
11
0
65
67
75
42
45
69
0
6
1,10-dibromodecane
7
bis[4-(bromomethyl)phenyl]methanone
4,40-carbonyldibenzoyl chloride
1,10-decanedioyl dichloride
8
9
10
11
12
bis[4-(bromomethyl)phenyl]methanone
4,40-carbonyldibenzoyl chloride
4,40-carbonyldibenzoyl chloride
22
68
a Synthesized using asymmetric precursor 5, as shown in Scheme 1.
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Table 2. Crystallographic Characteristics of Bridged Molecular Gyroscopes
compound
space group
asymmetric unit
Z
propeller chirality
packing coefficient
3
P1
C78H88O6
2
(M, M)/(P, P)
0.732
1.5 (C6H5CH3)
0.15 (C6H6)
C58H52O2
6
7
C2/c
P1
4
2
(M, M)/(P, P)
(M, M)/(P, P)
0.715
0.679a
C63H44O3
0.7 (CH2Cl2)
C63H40O5
8
P1
2
(M, M)/(P, P)
0.719
0.3 (C4H10O)
0.7 (CH2Cl2)
C58H48O4
9
C2/c
P1
4
2
(M, M)/(P, P)
(M, P)
0.798
0.703
10
C93H63O9
1.5 (C4H10O)
4.5 (CH2Cl2)
a SQUEEZE theorem was applied to remove undeterminable disordered solvent in the crystal.
“monomer” 8 and “dimer” 12. Compound 8 was found to have a
diffusion coefficient of log(ꢀ9.26) m2/s whereas the larger
compound 12 has a value of log(ꢀ9.40) m2/s. Compound 9
was also identified and characterized from its 1H and 13C NMR
which were consistent with the expected structure.
Single Crystal X-ray Diffraction Analyses. X-ray quality
single crystals of compound 9 were grown by slow evaporation
from a 50:50 mixture of benzene and toluene. Single crystals of 6
and 10 and single crystal solvates of 7 and 8 were obtained by
slow evaporation of 50:50 mixtures of dichloromethane and
diethyl ether. The crystal structure for the trialkyl-bridged
compound 3 was described previously,14 and diffraction quality
single crystals of 12 could not be obtained. Data acquisition for
crystals of compounds 6ꢀ10 was carried out at 100 K. A
summary of the space groups, asymmetric unit contents, mol-
ecules per unit cell, trityl chirality, and packing coefficients are
included in Table 2.
As shown in Table 2, all of the bridged molecular gyroscopes
Figure 4. Space-filling models of pairs of molecular gyroscopes 10 (left)
and 8 (right) illustrating the complementary face-to-edge interactions of
their 6-fold (6PE) and 4-fold (4PE) phenyl embraces, respectively. With
phenyl embraces on both sides of their structure, molecular gyroscopes
align in infinite chains.
crystallize in centrosymmetric space groups in low symmetry
triclinic (P1) or monoclinic (C2/c) crystal systems. Like the
crystal structure of trialkyl bridged compound 3, crystals of
molecular gyroscopes 7, 8, and 10 were found to contain
disordered solvent molecules with partial occupancies in the
unit cell. In fact, some of the solvent could not be accounted for in
the case of 7, and the structure had to be solved using the squeeze
theorem to remove the most highly disordered solvent molecules
in the structure. Only the alkyl monobridged compounds 6 and 9
crystallize without solvent in the structure. It is also notable that
all but compound 10 adopt conformations with both trityl
propellers in every molecule adopting homochiral helical con-
figurations, either (M, M) or (P, P). However, as required by the
space group, each crystal is racemic with both enantiomers
related by the symmetry operations in the unit cell.
a similar packing coefficient in the range of 0.703ꢀ0.798, which is
a common value for molecular crystals. The packing structures of
the bridged molecular gyroscopes take advantage of aromatic
edge-to-face interactions between adjacent trityl stators in the
form of distorted 6-fold and 4-fold phenyl embraces.19 The 6-fold
(6PE) and 4-fold phenyl embraces (4PE) are illustrated in
Figure 4 with molecular gyroscopes 10 and 8, respectively.
An ideal 6PE positions the triphenylmethyl groups in a config-
uration where every ring directs its own edge to the π-face of a ring
in the interacting trityl group partner, while its own π-face interacts
with the edge of another ring of the same trityl neighbor. It is well-
known that the complementary edge-to-face interactions of the
Packing coefficients calculated by the group increment meth-
od described by Gavezzotti17 showed no apparent correlation
with the number of bridges, even though the triply bridged
molecular gyroscopes were initially expected to have more empty
space. The packing coefficient (Ck) is a measure of crystal density
obtained by computing the relation between the van der Waals
form XPh3 Ph3X are quite robust and result in linear arrays that
3 3 3
in the ideal case possess a local S6 point group.19 The 6PE of
molecular gyroscopes 3, 7, 9, and 10 are locally distorted, some
with the presence of solvent molecules. The interaction observed
in the case of monobridged benzophenone diether, 7, resembles a
6PE, but the chain-like alignment between adjacent molecules is
volume of all the molecules in the unit cell (Z Vmol) divided by
3
the unit cell volume (Ck = (Z Vmol)/Vu-cell). As shown inTable 2,
3
all the structures solved without the SQUEEZE18 algorithm have
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Figure 7. Crystal structures of 3 viewed down the principal axis
illustrating the formation of layers orthogonal to the molecular rotor
axis. The figure also illustrates how next neighbors interdigitate by
directing one of the three bridges on one structure (in green) into the
vicinity of the rotator of another molecule.
into the space of the rotator. This collapse is clearly visible in
Figure 6 for the benzophenone on the left side of the first
molecule from the left.
Figure 5. View of the crystal structures of the four singly bridged
molecular gyroscopes 6, 7, 8, and 9. All four monobridged molecular
gyroscopes adopted an interdigitated packing motif where the trityl
group of one molecule approaches the phenylene rotator of an adjacent
molecule in the lattice. Hydrogen atoms and solvent molecules have
been omitted for clarity.
The molecular structures of all the molecular gyroscopes
present deviations from their maximum possible symmetry.
The three phenyl blades of each trityl propeller have different
torsion angles, and the alkyne axles are not straight and collinear.
The alkyne axles in the structure of 6 deviate from linearity with
angle of 178°, which reaches the largest value of 173.4° for the
structure of 7 and has an average value of 176.6° for all the
structures determined in this study. Some interesting differences
are observed between the various types of bridges. The thin
diether alkyl bridges in molecular gyroscopes 3 and 6 extend
radially outside the center of the molecule, leaving the proximity
of the rotator interdigitated with neighboring bridges or stators
and occupied with solvent molecules. The alkyl diester bridges of
compound 9 tend to collapse at the center, occupying two
disordered positions. Similarly, the bridging benzophenone
diether in compound 7 and one of the three bridges in compound
10 tend to adopt conformations that collapse toward the rotator,
seemingly to take advantage of aromaticꢀaromatic interactions.
One may conclude that benzophenone bridges do not provide
the molecular gyroscopes with sufficient shielding to prevent the
inclusion of solvent molecules or the interdigitation of bridges
from next neighboring molecules.
Figure 6. Space-filling model of triply benzophenone-bridged molecu-
lar gyroscopes 10 with the phenylene rotators in red, the trityl stators in
blue, and the benzophenone bridges in green, illustrating the formation
of layers.
mediated by solvent molecules rather than by edge-to-face inter-
actions. As shown in Figure 4, the 4-fold phenyl embrace of
molecular gyroscope 8 has one phenyl ring from each adjacent
molecule directed away, so that only four rings are involved in self-
complementary edge-to-face interactions. A common character-
istic of all four monobridged structures, 6ꢀ9, is that their “infinite”
chains of molecules aligned by their 6PE and 4PE are displaced
along the chain axis in a manner that the trityl group of one
molecule tends tooccupythe space thatis available near the rotator
of an adjacent molecule in the lattice (Figure 5).
In remarkable contrast, the structures of the triply bridged
molecular gyroscopes 3 and 10 have their 6PE chains in register
so that molecular gyroscopes occur in layers (Figure 6). The
space in the tribridged structures is filled by positioning the
bridges of a given molecule into the space left by the two bridges
of an adjacent one (Figure 7), and in the case of the triply bridged
benzophenone derivative 10, by collapsing one of the bridges
’ CONCLUSIONS
We have shown that the one-step triple-bridging procedure
using a hexaphenol precursor works when the bridging groups
are rigid and the two reaction sites extend beyond the distance
needed for “zonal” macrocyclization within a given trityl stator.
It is interesting that the yield per bond formed is not altered
significantly, as the structure varies from one to three bridges,
suggesting that there is no unfavorable strain introduced after
the first or second bridges are formed. It was also shown that
bridging reactions that form ether bonds are almost twice as
efficient as bridging reactions that form esters. While it is
notable that reasonably good quality crystals were obtained
for all molecular gyroscopes, it was shown that the linked diaryl
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benzophenone bridges are not sufficiently bulky to prevent inter-
digitation nor the inclusion of solvent molecules. It is also
important to note that there are torsional degrees of freedom
present in the structure of the bridge that allows it to collapse
toward the central rotator. All the lessons learned in this study will
be used to design the next generation of triply bridged molecular
gyroscopes.
stirred for an additional 12 h. The reaction was quenched with water and
partitioned with diethyl ether. The organic phase was washed with water
(3 ꢁ 50 mL) and brine (50 mL). The combined organic fractions were
dried over MgSO4 and concentrated on a rotary evaporator. The crude
product was then purified by recrystallization in 70:30 hexanes:diethyl
ether to afford clear crystals in 100% yield: mp = 91ꢀ92 °C. 1H NMR
(400 MHz, CDCl3): δ 7.31ꢀ7.36 (m, 10H, phenyl-H), 7.23 (apparent t,
J = 8.2, 7.8 Hz, 1H, H10), 6.88 (dd, J = 2.6, 1.8 Hz, 1H, H7), 6.83 (ddd,
J = 7.8, 1.8, 0.9 Hz, 1H, H9), 6.81 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H, H11),
3.75 (s, 3H, methoxy-H), 2.79 (s, 1H, OH); 13C NMR (100 MHz,
CDCl3): δ 159.3, 148.5, 146.7, 128.8, 127.9, 127.9, 127.3,120.5, 114.0,
112.4, 82.0, 55.2. FTIR (solid, HATR, cmꢀ1): 3462, 3071, 3008, 2972,
1595, 1489, 1463, 1448, 1414, 1361, 1318, 1244, 1166, 1148, 1032, 1013,
930, 869, 820, 794, 753, 699. HRMS (ESI) C20H18O2. Calcd: 290.13.
Found: 273.129 (loss of OH).
Synthesis of 3-(3-Methoxyphenyl)-3,3-diphenylpropyne
15. A 500 mL round-bottom flask equipped with a magnetic stir bar
was charged with mono-m-methoxy trityl alcohol 14 (4.6 g, 16.6 mmol)
and acetyl chloride (10 mL) and heated to reflux for 1 h. Excess acetyl
chloride was removed via rotary evaporator, washed with dry benzene
(3 ꢁ 20 mL), and concentrated on a rotary evaporator. The residue was
dissolved in dry benzene (50 mL), and (100 mL) 0.5 M ethynylmagne-
sium bromide in THF was added under argon and stirred overnight at
room temperature. Afterward, the reaction was quenched with aqueous
saturated ammonium chloride solution and partitioned with diethyl
ether. The organic phase was washed with water (2 ꢁ 50 mL) and brine
(1 ꢁ 50 mL). The combined organic fractions were dried over Mg2SO4,
filtered, and concentrated on a rotary evaporator. The residue was then
purified by flash chromatography on silica gel (2:1 hexanes:DCM) to
afford 83% yield of a yellow oil. 1H NMR (400 MHz, CDCl3):
δ 7.2ꢀ7.35 (m, 10H, phenyl-H), 7.22 (apparent t, J = 8.2, 7.8 Hz, 1H,
H10), 6.88 (dd, J = 2.5, 1.8 Hz, 1H, H7), 6.83 (ddd, J = 7.8, 1.8, 0.9 Hz,
1H, H9), 6.81 (ddd, J= 8.2, 2.5, 0.9 Hz, 1H, H11), 3.74 (s, 3H, methoxy-H),
2.78 (s, 1H, H3); 13C NMR (100 MHz, CDCl3): δ 159.3, 146.3, 144.6,
129.0, 128.8, 128.0, 126.9, 121.7, 115.4, 111.9, 89.6, 73.4, 55.5, 55.1.
FTIR (solid, HATR, cmꢀ1): 3289, 3057, 2932, 2833, 1594, 1486, 1462,
1444, 1423, 1317, 1249, 1171, 1143, 1037, 967, 913, 866, 813, 786, 748,
697. HRMS (ESI) C22H18O. Calcd: 298.135. Found: 273.125 (loss of
terminal alkyne).
Synthesis of 1,4-Bis[3-(3-methoxyphenyl)-3,3-diphenyl-
propynyl]benzene 16. A 250-mL oven-dried round-bottom flask
equipped with a magnetic stir bar was charged with mono-m-methoxy
trityl alkyne 15 (1.1 g, 3.69 mmol), diiodobenzene (607 mg, 1.89 mmol),
diisopropylamine (5 mL), and dry THF (10 mL), and the solution was
degassed with argon for 30 min. CuI (35 mg, 0.18 mmol) and Pd-
(PPh3)2Cl2 (130 mg, 0.18 mmol) were added, and the reaction was
heated to reflux for 24 h. The reaction was quenched with aqueous
saturated ammonium chloride and partitioned with diethyl ether. The
organic phase was washed with water (2 ꢁ 40 mL) and brine (40 mL).
The combined organic fractions were dried over MgSO4, filtered, and
concentrated on a rotary evaporator. The residue was then purified by
flash chromatography onsilica gel (2:1 hexanes:DCM) toafford 73% yield
ofa yellowsolid:mp= 204ꢀ205 °C. 1H NMR(300 MHz, CDCl3): δ 7.36
(s, 4H, H2), 7.21ꢀ7.31 (m, 20H, phenyl-H), 7.15 (apparent t, J = 8.2, 7.8
Hz, 2H, H10), 6.84 (dd J = 2.6, 1.5 Hz, 2H, H7), 6.81 (ddd, J = 7.8, 1.8, 0.9
Hz, 2H, H9), 6.76 (dd, J = 8.2, 2.5, 0.9 Hz, 2H, H11), 3.66 (s, 6H,
methoxy-H); 13C NMR (75 MHz, CDCl3): δ 159.3, 146.8, 145.0, 131.4,
129.1, 128.9, 128.0, 126.9, 123.2, 121.8, 115.5, 112.0, 97.2, 84.8, 56.2, 55.1.
FTIR (solid, HATR, cmꢀ1): 3051, 2952, 2924, 2829, 1601, 1579, 1489,
1445, 1430, 1315, 1290, 1241, 1137, 1032, 881, 842, 780, 767, 756, 717.
HRMS (MALDI-ICR) C50H38O2. Calcd: 670.287. Found: 670.284.
Synthesisof 1,4-Bis(3-(3-hydroxyphenyl)-3,3-diphenylpropy-
nyl)benzene 17. A 250 mL round-bottom flask equipped with magnetic
stir bar was charged with dimethoxy-rotor 16 (600 mg, 0.89 mmol) and dry
’ EXPERIMENTAL SECTION
IR spectra were obtained with a Perkin-Elmer spectrum 100 HATR-
FTIR instrument. 1H and 13C NMR spectra were acquired on a Br€uker
NMR spectrometer at 400 and 100 MHz or 300 and 75 MHz,
respectively, with CDCl3 as the solvent. NMR coupling constants were
calculated using gNMR. All the NMR assignments described below are
based on the atom numbering shown in Scheme 3. Mass spectra were
acquired on an Applied Biosystems Voyager-DE-STR MALDI-TOF.
The 3-bromoanisole, benzophenone, 2.5 M n-butyllithium in hexanes,
acetyl chloride, 0.5 M ethynylmagnesium bromide in THF, diisopropyl-
amine, CuI, bis(triphenylphosphine)palldium(II) chloride, 1,4-diiodo-
benzene, 1,10-dibromodecane, decandioyl chloride, 1 M boron tribro-
mide in DCM, and potassium carbonate were commercially available
and were used without further purification. THF and benzene were
distilled from sodium and kept under argon. Samples of bis[4-(bromo-
methyl)phenyl]methanone (for the synthesis of 7 and 10) and 4,40-car-
bonyldibenzoyl chloride (for the synthesis of 8 and 12) were prepared as
described in the literature.20 The synthesis and characterization of 3 has
been described previously.14
General Synthesis of Monobridged Molecular Gyro-
scopes. An oven-dried 100 mL round-bottom flask was charged with
potassium carbonate (0.92 mmol) and dry DMF (20 mL) under an
argon atmosphere. Compound 17 (0.127 mmol) and the respective
bridge precursor (0.127 mmol) were added into two separate oven-dried
10 mL round-bottom flasks and dissolved in dry DMF (4 mL).
Compound 17 and the coresponding bridge precursor were added via
syringe slowly at 0.5 mL/h over 8 h to the flask containing potassium
carbonate and dry DMF at 40 °C, and the mixture was left to react
overnight. Afterward, the solution was quenched with a saturated
ammonium chloride solution (20 mL) and partitioned with ethyl
acetate. The organic phase was washed with saturated lithium chloride
(3 ꢁ 10 mL) and then brine (20 mL). Combined organic fractions were
dried over MgSO4 and concentrated on a rotary evaporator. The residue
was then purified by flash chromatography on silica gel.
General Synthesis of Tribridged Molecular Gyroscopes.
An oven-dried 100 mL round-bottom flask was charged with potassium
carbonate (1.52 mmol) and dry DMF (20 mL) under an argon atmo-
sphere. Compound 1 (0.127 mmol) and the respective bridge (0.382
mmol) were added into two separate oven-dried 10 mL round-bottom
flasks and dissolved in dry DMF (4 mL). Compound 1 and the
coresponding bridge precursor were added via syringe slowly at
0.5 mL/h over 8 h to the flask containing potassium carbonate and
dry DMF at 50 °C and stirred overnight. After 24 h, the solution was
quenched with saturated ammonium chloride (20 mL) and partitioned
with ethyl acetate. The organic phase was washed with saturated lithium
chloride (3 x10 mL) and brine (20 mL). Combined organic fractions
were dried over MgSO4 and concentrated on a rotary evaporator. The
residue was then purified by flash chromatography on silica gel.
Synthesis of (3-Methoxyphenyl)diphenylmethanol 14. An
oven-dried 500 mL round-bottom flask was charged with 3-bromoani-
sole 13 (23.1 g, 0.125 mol), dry THF (500 mL) under argon, and cooled
to ꢀ78 °C in dry ice/acetone bath. Then 2.5 M n-BuLi (50 mL) in
hexanes was added to the reaction and stirred for 30 min. Afterward,
benzophenone (22.7 g, 0.125 mol) dissolved in 40 mL of dry THF was
added to reaction at ꢀ78 °C, allowed to warm to room temperature, and
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The Journal of Organic Chemistry
ARTICLE
DCM (10 mL) under argon atmosphere. The flask was cooled to 0 °C in an
ice bath, and 1 M BBr in DCM (3.58 mL) was added. The reaction was
stirred for 3 h at 0 °C, quenched by addition of ice, and partitioned with
diethyl ether and water. The organic phase was washed with saturated sodium
bicarbonate (2 ꢁ 20 mL) and brine (20 mL). Combined organic fractions
were dried over MgSO4, filtered, and concentrated on a rotary evaporator.
The residue was purified by flash chromatography on silica gel (3:1 hexanes:
acetone) to afford a yellow powder in 78% yield: mp = 250ꢀ252 °C. 1HNMR
(400 MHz, CDCl3): δ 7.44 (s, 4H, H2), 7.21ꢀ7.40 (m, 20H, phenyl-H),
7.16 (apparent t, J= 8.2, 7.8 Hz, 2H, H10), 6.87 (ddd, J= 7.8, 1.8, 0.9 Hz, 2H,
H9), 6.78 (dd, J = 2.5, 1.8 Hz, 2H, H7), 6.76 (ddd, J = 8.2, 2.5, 0.9 Hz, 2H,
H11); 13C NMR (100 MHz, CDCl3): δ 155.4, 147.0, 145.0, 144.2, 131.4,
129.1, 128.0, 126.9, 123.1, 121.7, 116.4, 114.0, 97.1, 84.8, 56.0. FTIR (solid,
HATR, cmꢀ1): 3531, 3343 (broad), 3058, 2923, 1596, 1489, 1446, 1263,
1031, 873, 783, 754, 697. HRMS (MALDI-ICR) C48H34O2. Calcd: 642.256.
Found: 643.264 (M + H)
Monoalkyl Ether-Linked Bridged Molecular Gyroscope 6.
A 46% yield of a white solid: mp = 230ꢀ232 °C. 1H NMR (400 MHz,
CDCl3): δ 7.53 (dd, J = 2.5, 1.8 Hz, 2H, H7), 7.44 (s, 4H, H2),
7.20ꢀ7.35 (m, 20H, phenyl-H), 7.11 (apparent t, J = 8.2, 7.8 Hz, 2H,
H10), 6.80 (ddd, J = 8.2, 2.5, 0.9 Hz, 2H, H11), 6.29 (ddd, J = 7.8, 1.8, 0.9
Hz, 2H, H9), 3.97 (t, J = 4.8 Hz, 4H, alkyl-H), 1.76 (quintet, J = 5.4, 4.8
Hz, 4H, alkyl-H), 1.42ꢀ1.44 (m, 4H, alkyl-H), 1.26ꢀ1.30 (m, 8H, alkyl-H);
13C NMR (75 MHz, CDCl3): δ 159.1, 146.5, 145.1, 131.4, 129.1, 125.5,
128.0, 126.9, 123.2, 121.1, 115.4, 113.7, 97.4, 84.8, 67.8, 56.3, 29.2, 29.2,
29.0, 25.9. FTIR (powder, HATR, cmꢀ1): 3063, 3019, 2925, 2853, 1724,
1597, 1489, 1446, 1251, 1033. HRMS (MALDI-ICR) C58H52O2. Calcd:
780.396. Found: 780.395
Tribenzophenone Ether-Linked Bridged Molecular Gyro-
scope 10. An 11% yield of white solid: mp = decomposes >379 °C. 1H
NMR (400 MHz, CDCl3): δ 7.66 (d, J = 8.0 Hz, 12H, benzophenone-H),
7.24 (d, J = 8.0 Hz, 12H, benzophenone-H), 7.23 (dd, J = 2.5, 1.8 Hz, 6H,
H7), 7.16 (apparent t, J = 8.2, 7.8 Hz, 6H, H10), 6.96 (ddd, J = 8.2, 2.5,
0.9 Hz, 6H, H11), 6.86 (s, 4H, H2), 6.42 (ddd, J = 7.8, 1.8, 0.9 Hz, 6H,
H9), 5.19 (s, 12H, methylene-H); 13C NMR (100 MHz, CDCl3):
δ 195.0, 158.0, 146.2, 142.1, 136.8, 131.2, 130.4, 128.8, 126.5, 122.9,
121.7, 115.8, 113.9, 95.9, 85.0, 68.7, 56.2. FTIR (powder, HATR, cmꢀ1):
3059, 2982, 2857, 2250, 1726, 1655, 1593, 1230, 731. HRMS (MALDI-
ICR) C93H64O9. Calcd: 1324.455. Found: 1347.447 (M+Na).
Monobenzophenone Ester-Linked Bridged Molecular
Gyroscope Dimer 12. A 22% yield of white solid: mp =
1
225ꢀ227 °C. H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 8.4 Hz,
8H, benzophenone-H), 8.27 (d, J = 8.4 Hz, 8H, benzophenone-H), 7.46
(s, 8H, H2), 7.42 (dd, J = 3.1, 2.3 Hz, 4H, H7), 7.25ꢀ7.40 (m, 44H,
phenyl-H and H10), 7.19 (ddd, J = 10.7, 3.1, 1.2 Hz, 4H, H11), 7.02
(ddd, J = 10.5, 2.3, 1.2 Hz, 4H, H9); 13C NMR (75 MHz, CDCl3): δ
195.1, 164.1, 150.6, 147.2, 144.6, 141.0, 133.1, 131.5, 130.2, 129.9, 129.1,
128.9, 128.2, 127.1, 126.7, 123.1, 122.5, 120.2, 96.8, 85.1, 56.1. FTIR
(powder, HATR, cmꢀ1): 3059, 1738, 1664, 1490, 1446, 1259, 1212,
1071, 905, 719. HRMS (ESI) C126H80O10. Calcd: 1752.575. Found:
1753.583(M + H).
’ ASSOCIATED CONTENT
S
Supporting Information. Spectroscopic data for all com-
b
pounds, and crystallographic information files (cif) for com-
pounds 6ꢀ9. This material is available free of charge via the
Internet at http://pubs.acs.org.
Monobenzophenone Ether-Linked Bridged Molecular
1
Gyroscope 7. A 57% yield of white solid: mp = 246ꢀ247 °C. H
NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.3 Hz, 4H, benzophenone H),
7.39 (d, J = 8.3 Hz, 4H, benzophenone-H), 7.28 (dd, J = 2.5, 1.8 Hz, 2H,
H7), 7.22ꢀ7.27 (m, 20H, phenyl-H), 7.22 (s, 4H, H2), 7.16 (apparent t,
J = 8.2, 7.8, 2H, H10), 6.96 (ddd, J = 8.2, 2.5, 0.9 Hz, 2H, H11), 6.34
(ddd, J = 7.8, 1.8, 0.9 Hz, 2H, H9), 4.79 (s, 4H, methylene-H); 13C NMR
(75 MHz, CDCl3): δ 195.8, 158.2, 146.4, 145.0, 142.2, 136.6, 131.3,
130.4, 129.1, 128.8, 128.0, 126.9, 126.4, 123.1, 121.9, 115.2, 115.0, 96.9,
84.7, 68.9, 56.2. FTIR (powder, HATR, cmꢀ1): 3051, 2956, 2916, 2849,
1670, 1260, 1008, 790, 697 cmꢀ1. HRMS (MALDI-ICR) C63H44O3.
Calcd: 848.329. Found: 871.320 (M + Na).
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: mgg@chem.ucla.edu.
Present Addresses
†Chemistry Department, University of Texas, 500 West University
Ave., El Paso, TX.
Monobenzophenone Ester-Linked Bridged Molecular
Gyroscope 8. An 18% yield of white solid: mp = decomposes
>411 °C. H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 8.4 Hz, 4H,
’ ACKNOWLEDGMENT
1
The National Science Foundation supported this work
through grant DMR-0605688 and creativity extension DMR-
0937243. P.C. acknowledges the National Science Foundation
IGERT: Materials Creation Training Program (DGE-0654431)
and the California Nanosystems Institute.
benzophenone-H), 7.84 (dd, J = 2.5, 1.8 H, 2H, H7), 7.72 (d, J = 8.4 Hz
4H, benzophenone-H), 7.58 (ddd, J = 8.2, 2.5, 0.9 Hz 2H, H11), 7.49
(s, 4H, H2), 7.26ꢀ7.35 (m, 22H, phenyl-H and H10), 6.76 (ddd, J =
7.8, 1.8, 0.9 Hz 2H, H9); 13C NMR (75 MHz, CDCl3): δ 196.5, 163.2,
151.0, 146.5, 144.7, 142.0, 133.1, 131.6, 130.1, 129.8, 129.0, 128.7, 128.2,
127.1, 126.4, 123.3, 121.3, 119.8, 96.7, 85.2, 56.1. FTIR (powder,
HATR, cmꢀ1): 3063, 2922, 2852, 1744, 1672, 1490, 1446, 1260,
1213, 1071, 905, 749, 695. HRMS (MALDI-ICR) C63H40O5. Calcd:
876.287. Found: 876.285 and 899.275 (M + Na)
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A 20% yield of white solid: mp = 318ꢀ319 °C. H NMR (400 MHz,
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