Synthesis of stable dodecaalkoxy derivatives of hypercloso-B 12H12

Article abstract of DOI:10.1021/ja0556373

The scope and limitations of the alkylation of [closo-B₁₂(OH) ₁₂]^2- using a series of fourteen alkyl and aralkyl halides and two p-toluenesulfonic acid esters in the presence of N,N- diisopropylethylamine have been investigated. The dodecaalkoxy-closo- dodecaborate products, [closo-B₁₂(OR)₁₂]^2-, and their hypercloso two-electron oxidation products have been explored. The species [closo-B₁₂(OR)₁₂]^2- containing 26 cage-bonding electrons may undergo two reversible, sequential, one-electron oxidation processes, producing a 25-electron radical anion and a 24-electron neutral species. Several oxidizing reagents were investigated for the chemical oxidation of [closo-B₁₂(OR)₁₂]^2- and [hypercloso-B₁₂(OR)₁₂]^- to [hypercloso-B ₁₂(OR)₁₂]. Both FeCl₃·6H₂O and K₃Fe(CN)₆ in 90/5/5 ethanol/acetonitrile/H ₂O were found to be the reagents of choice. The reverse reaction leading from the neutral species to the radical anion and subsequently to the dianion was achieved using sodium borohydride in ethanol. A variety of alkoxyl derivatives have been synthesized by heating the reactants for extended periods of time in acetonitrile at the reflux temperature. The use of elevated reaction temperatures attained by employing moderate argon pressure (autoclave) over the reaction mixture led to drastic reductions in reaction times and increased efficiency. X-ray diffraction studies of substituted dodecabenzyl ether derivatives proved that 2^2- has approximate I_h symmetry while hypercloso-2, -3, -9, -11, -12, and -13 have approximate D_3d point group symmetry due to Jahn-Teller distortion from I_h.

Full text of DOI:10.1021/ja0556373

Published on Web 12/03/2005
Synthesis of Stable Dodecaalkoxy Derivatives of
hypercloso-B12H12
Omar K. Farha, Richard L. Julius, Mark W. Lee, Ramon E. Huertas,
Carolyn B. Knobler, and M. Frederick Hawthorne*
Contribution from the Department of Chemistry and Biochemistry, UniVersity of California,
Los Angeles, 607 Charles E. Young DriVe East, Los Angeles, California 90095-1569
Received August 17, 2005; E-mail: mfh@chem.ucla.edu
Abstract: The scope and limitations of the alkylation of [closo-B12(OH)12]2- using a series of fourteen alkyl
and aralkyl halides and two p-toluenesulfonic acid esters in the presence of N,N-diisopropylethylamine
have been investigated. The dodecaalkoxy-closo-dodecaborate products, [closo-B12(OR)12]2-, and their
hypercloso two-electron oxidation products have been explored. The species [closo-B12(OR)12]2- containing
26 cage-bonding electrons may undergo two reversible, sequential, one-electron oxidation processes,
producing a 25-electron radical anion and a 24-electron neutral species. Several oxidizing reagents were
investigated for the chemical oxidation of [closo-B12(OR)12]2- and [hypercloso-B12(OR)12]- to [hypercloso-
.
B12(OR)12]. Both FeCl3 6H2O and K3Fe(CN)6 in 90/5/5 ethanol/acetonitrile/H2O were found to be the reagents
of choice. The reverse reaction leading from the neutral species to the radical anion and subsequently to
the dianion was achieved using sodium borohydride in ethanol. A variety of alkoxyl derivatives have been
synthesized by heating the reactants for extended periods of time in acetonitrile at the reflux temperature.
The use of elevated reaction temperatures attained by employing moderate argon pressure (autoclave)
over the reaction mixture led to drastic reductions in reaction times and increased efficiency. X-ray diffraction
studies of substituted dodecabenzyl ether derivatives proved that 22- has approximate Ih symmetry while
hypercloso-2, -3, -9, -11, -12, and -13 have approximate D3d point group symmetry due to Jahn-Teller
distortion from Ih.
Scheme 1. Synthetic Routes to Ester and Ether Closomers8,9
Introduction
Molecules with organic chains extending and branching from
a rigid and compact spherical molecular platform have been
attractive targets for synthesis and exploitation involving novel
materials and biosciences applications. A potential platform
precursor that may fulfill these requirements and potentially
furnish a redox-active core is the icosahedral [closo-B12H12]2-
ion.1 The fascinating dianionic closo-boranes are a widely
studied class of polyhedral boron clusters. In the cases of [closo-
B12H12]-2 and [closo-B10H10]-2, their high stability, delocalized
bonding, and ease of electrophilic B-H substitution suggest
their description as three-dimensional species2 not unlike
aromatic hydrocarbons.
The discovery of the BH hydroxylation reaction leading to a
variety of polyhedral borane and carborane structures such as
[closo-CHB11(OH)11]- and [closo-1,12-C2H2B10(OH)10] and
most often exemplified by the conversion of [closo-B12H12]-2
to [closo-B12(OH)12]-2, 1, has revealed a new dimension in the
chemistry of polyfunctional and redundantly substituted small
molecules.3-10 This is possible due to the facile derivatization
of the B-OH vertexes in essentially the same fashion as
alcohols using reactions in which the oxygen center is a
nucleophile which reacts without B-O bond-breaking. Thus,
12-fold carboxylate ester8,10 and ether9 derivatives, now defined
as closomers,8,11 are available, and improved synthesis routes
leading to the latter derivatives are described here. Scheme 1
(3) Peymann, T.; Herzog, A.; Knobler, C. B.; Hawthorne, M. F. Angew. Chem.,
Int. Ed. 1999, 38, 1062.
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Soc. 2001, 123, 2182.
(6) Hawthorne, M. F.; Peymann, T.; Herzog, A. H. U.S. Patent 6,323,372,
2001.
(1) (a) Pitochelli, A. R.; Hawthorne, M. F. J. Am. Chem. Soc. 1960, 82, 3228.
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A230, 110.
(2) (a) Hoffman, R.; Lipscomb, W. N. J. Chem. Phys. 1962, 38 (8), 2179. (b)
Hawthorne, M. F. AdVances in Boron Chemistry; Special Publication No.
201; Royal Society of Chemistry: London, 1997; Vol. 82, p 261.
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(10) Thomas, J.; Hawthorne, M. F. Chem. Commun. 2001, 18, 1884.
9
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J. AM. CHEM. SOC. 2005, 127, 18243-18251
18243

A R T I C L E S
Farha et al.
presents representative reactions leading to closomers previously
reported8,9 and expanded here as well as in an upcoming paper.12
As previously pointed out,8-10 closomer derivatives of 1 share
some of the same characteristics as dendrimers. The principal
differences are the smaller size, greater rigidity (dendrimers are
more loosely constructed while closomers of the same func-
tionality are more rigidly configured since 12 chains simulta-
neously originate at the icosahedral surface in close proximity
to each other), higher symmetry, monodispersity, and much
more compact presentation of functional groups seen with
closomer derivatives of 1 as compared to dendrimer structures
having the same, or similar, 12-fold functionality. In addition,
derivatives of 1 can be obtained in which 1 plays the role of a
dendrimer core providing 12-fold reactivity in the first genera-
tion. However, the differences between the conventional den-
drimer structure and the corresponding derivatives of 1 appeared
to be sufficiently great as to warrant a distinction between the
two in nomenclature. Consequently, the relatively small poly-
functional derivatives of 1 have been designated as “closomers”
to emphasize these distinctions. This unofficial nomenclature
scheme is described fully elsewhere.8,11
Figure 1. ORTEP diagram of dodeca(benzyloxy)dodecaborane dianion
(22-) having an approximate Ih symmetry.9
As will be shown in detail in an upcoming paper,13 the ether-
linked closomers presented here have the unique property of
undergoing facile and reversible one-electron redox reactions
involving the parent closomer B122- core structure. Thus, species
2-
-
containing the B12 (26 electrons), B12 (25 electrons), and
neutral B12 (24 electrons) core structures are easily inter-
converted using chemical or electrochemical redox reactions.
The two one-electron redox processes of 2 belonging to the
{[B12(OBn)12]2-/{[B12(OBn)12]1-} and {[B12(OBn)12]1-/{[B12-
(OBn)12]} couples have E1/2 values of 0.06 and 0.56 V versus
AgCl, respectively. The 24- and 25-electron species are
stabilized by back-bonding to the electron-deficient B12 core
by nonbonding electrons available on each of the 12 ether
oxygen substituents. X-ray diffraction studies using the dode-
cabenzyl ether system proved that 22- and 21- have approximate
Ih symmetry while 2 exhibits approximate D3d symmetry due
to Jahn-Teller distortion.9 The ORTEP structures of 22- and
2, along with representative B-B and B-O bond lengths
observed in 2, are presented in Figures 1 and 2 and Table 2,
respectively. The B-B distances designated as a six-pointed
star in the structure of 2 (Figure 2) are long compared to
comparable distances found in 22-, while B-O distances
observed at these same B atoms are shortened relative to those
observed in 22-. This shortening is attributed to back-bonding
of nonbonding ether oxygen electrons with the electron-deficient
D3d cage. Therefore, the cages of 22-, 21-, and 2 have the
property of a pseudometal center characterized by redox
reactions and stabilization of electron-deficient oxidation states
by back-bonding of substituent nonbonding electrons. Addition-
ally, the crystal structures of 3 and 9 shown in Figure 3 and 4
exhibited approximate D3d symmetry and confirmed the assign-
ment of this point group to 2.
Figure 2. ORTEP diagram of dodeca(benzyloxy)dodecaborane (2) with
distorted icosahedral (an approximate D3d) symmetry.9
reported by McKee.14 These results supported the existence of
the two observed reversible one-electron oxidation reactions of
the B12 core as well as the 11B NMR chemical shifts of the
dianion and neutral ether closomers. In addition, a 11B downfield
shift of 51.6 ppm is predicted on going from [closo-B12(OR)12]2-
to [hypercloso-B12(OR)12]. This is in excellent agreement with
the experimental values of 54-58 ppm observed throughout
this study. The DFT description of 2 at the AM1 level predicted
a Th structure to be 13.2 kcal/mol more stable than a D3d
structure. Conversely, Fujimori and Kimura15 predicted from
energy minimization computations carried out at the HF/6-31G-
(d) level for hypercloso-B12H12 that an undistorted icosahedral
structure would have partially occupied 4-fold degenerate
Following the initial publications concerning closomer chem-
istry,8,9 the application of density functional theory to anionic
and neutral persubstituted 12-vertex boron cage systems was
(11) Hawthorne, M. F. Pure Appl. Chem. 2003, 75, 1157.
(12) Li, T.; Jalisatgi, S. S.; Bayer, M. J.; Maderna, A.; Khan, S. I.; Hawthorne,
M. J. Am. Chem. Soc., in press.
(13) Farha, O. K.; Lee, M. W.; Julius, R. L.; Hansch, C.; Hawthorne, M. F. J.
Am. Chem. Soc., to be submitted for publication.
(14) McKee, M. Inorg. Chem. 2002, 41, 1299.
(15) Fujimori, M.; Kimura, K. J. Solid State Chem. 1997, 133, 178.
9
18244 J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005

Synthesis of Derivatives of hypercloso-B12H12
A R T I C L E S
phores,25 radionuclide chelators,26-29 and other biomedical
applications.30-39 Dendrimers have been employed in many of
these applications; their syntheses by either convergent40 or
divergent41 pathways can be difficult to control, resulting in
polydispersity. In this paper we expand upon the original paper9
and further describe the synthesis, purification, and characteriza-
tion of monodispersed ether-linked closomers.
Results and Discussion
The original paper on ether-linked closomers9 was ac-
companied by a paper describing closomers linked by carboxy-
late ester bonds.8 An additional brief paper described a
nanoparticle created for use as a boron neutron capture therapy
agent comprised of 12 [nido-7,8-C2B9H11]- anions attached
through carboxylate ester spacer groups to an icosahedral B12
core.10 Recent advances in ester closomers will be forthcoming
in a separate paper.12
Figure 3. ORTEP diagram of the structure of dodecaethoxy-hypercloso-
dodecaborane (3) crystallized from methanol.
2-
Since the original publication of this work,9 the hydroxylation
of Cs2[closo-B12H12] to produce Cs2-1 has been markedly
improved to give yields of 95% or greater.4 Although previously
predicted to be unstable,14 Cs2-1 exhibited remarkable thermal
stability as heating for 2 days at 200 °C in acetonitrile gave no
evidence of decomposition. This work rests upon the earlier
sequential hydroxylation of Cs2[closo-B12H12] with aqueous H2-
SO4 to produce, at will, a single isomer of Cs2[closo-B12H12-n
-
(OH)n] (n ) 1-4 inclusive).42,43 The latter species were
subsequently explored in unpublished reactions with electro-
philic reagents such as alkyl halides, acyl chlorides, alkane-
sulfonyl chlorides, phenyl isocyanate, and titanocene dichloride,
and they may serve as precursors for more complex structures.
Alkylation of [closo-B12(OH)12]2-. A new and improved
method for the synthesis and isolation of ether-linked closomers
has been established by the alkylation of (TBA)2-1 [TBA )
Figure 4. ORTEP diagram of the structure of dodeca(4-fluorobenzyloxy)-
hypercloso-dodecaborane (9) crystallized from toluene.
(20) Carter, F. L.; Siatkowski, R. E.; Wohljen, H. Molecular Electronic DeVices;
North-Holland: Amsterdam, 1988.
(21) (a) Miedaner, A.; Curtis, C. J.; Barkley, R. M.; DuBois, D. L. Inorg. Chem.
1994, 33, 5482. (b) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1526. (c) Chow, H. F.; Mak, C. C. J. Org.
Chem. 1997, 62, 5116. (d) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick,
K. S. J. Am. Chem. Soc. 1996, 118, 5708.
(22) (a) Balzani, V.; Scandola, F. Supramolecular Photochemistry; Horwood:
Chichester, U.K., 1991. (b) Lehn, J.-M. Supramolecular Chemistry; VCH:
Weinheim, Germany, 1995.
(23) Thomas, G. D. Methods Mol. Med. 2000, 25, 97.
(24) Reddy, J. A.; Low, P. S. Crit. ReV. Ther. Drug Carrier Syst. 1998, 15,
587.
(25) Haugland, R. P. Fluorescent Labels; Humana Press: Totowa, NJ, 1991.
(26) Weiner, R. E.; Thakur, M. L. Radiochim. Acta 1995, 70-1, 273.
(27) Buchsbaum, D. J. Cancer 1997, 80, 2371.
HOMOs, and a Jahn-Teller distortion to D3d symmetry was
predicted.
Other examples of icosahedral borane derivatives which
violate Wade’s 2n + 2 electron-counting rule16 (n ) number
of vertexes) are [hypercloso-B12(CH3)12]-,17 [hypercloso-CB11-
(CH3)12],18 and hypercloso-BxClx (x ) 4, 7-12).19 The unusual
electron count can be stabilized by the exo-halogen substituents
which supply additional electron density to the cage through
π-back-bonding of nonbonded electrons or through hypercon-
jugation between the methyl substituents and cage.18 Steric
protection and electron donation from the substituents (ether
oxygen) are responsible for the unusual stability of the ether
closomers. Novel closomers based upon carboxylate ester
structures,8,10 which are not capable of hypercloso cage stabi-
lization, will be presented in an upcoming paper.12
(28) Hawthorne, M. F.; Maderna, A. Chem. ReV. 1999, 99, 3421.
(29) Anderson, C. J.; Lewis, J. S. Expert Opin. Ther. Pat. 2000, 10, 1057.
(30) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem. ReV. 1999,
99, 2293.
(31) Wender, P. A.; Mitchell, D. J.; Pattabiraman, K.; Pelkey, E. T.; Steinman,
L.; Rothbard, J. B. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 13003.
(32) Rajski, S. R.; Williams, R. M. Chem. ReV. 1998, 98, 2723.
(33) Nilsson, F.; Tarli, L.; Viti, F.; Neri, D. AdV. Drug DeliVery ReV. 2000, 43,
165.
(34) Latham, P. W. Nat. Biotechnol. 1999, 17, 755.
(35) Zanini, D.; Roy, R. Bioconjugate Chem. 1997, 8, 187.
(36) Tam, J. P. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 5409.
(37) Bielinska, A.; Kukowska-Latallo, J. F.; Johnson, J.; Tomalia, D. A.; Baker,
J. R., Jr. Nucleic Acids Res. 1996, 24, 2176.
While applications of redox-active ether-linked closomers
have not been fully developed at this time, in this paper and an
upcoming paper,13 it is suggested that they may find applications
including molecular electronics,20 electrocatalysis,21 information
storage,22 components in drug delivery systems,23,24 fluoro-
(38) Shockley, T. R.; Lin, K. E.; Nagy, J. A.; Tompkins, R. G.; Dvorak, H. F.;
Yarmush, M. L. Ann. N. Y. Acad. Sci. 1991, 618, 367.
(39) George, A. J. T.; Urch, C. E. Diagnostic and Therapeutic Antibodies;
Humana Press: Totowa, NJ, 2000.
(40) Hawker, C. J.; Fre`chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638.
(41) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III. Angew. Chem., Int.
Ed. Engl. 1990, 29, 138.
(16) Wade, K. D. AdV. Inorg. Chem. Radiochem. 1976, 18, 1.
(17) Peymann, T.; Knobler, C. B.; Hawthorne, M. F. Chem. Commun. 1999,
2039.
(42) Knoth, W. H.; Sauer, J. C.; England, D. C.; Hertler, W. R.; Muetterties, E.
L. J. Am. Chem. Soc. 1964, 86, 3973.
(18) King, B. T.; Janousek, Z.; Gruener, B.; Trammell, M.; Noll, B. C.; Michl,
J. J. Am. Chem. Soc. 1996, 118, 3313.
(43) Peymann, T.; Knobler, C. B.; Hawthorne, M. F. Inorg. Chem. 2000, 39,
1163.
(19) Morrison, J. Chem. ReV. 1991, 91, 35
9
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A R T I C L E S
Farha et al.
Scheme 2. An Ether Closomer Side Reaction Leading to
Table 1. Methods and Conditions Employed for Ether Closomer
Synthesis
Closomer Oxidation and Radical Formation Where R ) Benzyl
closomer
ether
R in
method/
reagenta
reaction time/ yieldb
(BOR)12
temp
(%)
2
benzyl
1/benzyl bromide
2/benzyl chloride
2/bromoethane
1/1-bromohexane
2/1-bromohexane
2/n-hexyl tosylate
1/1-bromopentane
2/1-bromopentane
1/allyl bromide
6 d/reflux
69
4 h/150 °C 65
12 h/150 °C 70
23 d/reflux 80
8 h/150 °C 75
2 h/150 °C 70
21 d/reflux 78
7 h/150 °C 75
temperature. In these studies identical reaction mixtures were
studied under both sets of conditions. A temperature of 150 °C
and pressures ranging from 500 to 1500 psi were arbitrarily
employed. Under these conditions, the reaction time was reduced
from many days to a few hours while good reaction yields were
maintained, demonstrating this procedure to be the method of
choice for the ether-linked closomer synthesis.
3
4
ethyl
hexyl
5
6
7
pentyl
allyl
7 d/reflux
55
2/allyl chloride
1/4-bromo-1-butene
2/4-bromo-1-butene
3 h /150 °C 60
19 d/reflux 65
6 h/150 °C 62
8 h /150 °C 75
3-butenyl
The previously described alkylation conditions (method 1)
were successfully applied to fourteen organic halides and two
p-toluenesulfonate esters. A 120-fold mole ratio of starting
reagent to (TBA)2-1 is essential for complete reaction in
acetonitrile at the reflux temperature and atmospheric pressure.
When the temperature was increased to 150 °C at elevated
pressure, the initial concentration of excess reagent was reduced
to an 18-fold mole ratio relative to that of (TBA)2-1 while the
reaction time was similarly reduced. As an example, allyl
chloride was chosen for the study of reaction time with respect
to initial reagent concentration. The reaction times obtained with
different initial concentrations of allyl chloride versus constant
(TBA)2-1 were determined at 150 °C. Completion of the reaction
was determined by employing 11B NMR spectra initially
observed as a symmetrical singlet near -18 ppm corresponding
to (TBA)2-1 and subsequently coalescing to a symmetrical
singlet near -16 ppm associated with [closo-B12(OR)12]2-. The
results showed that the necessary time for complete reaction
decreased with increasing initial allyl chloride concentration,
and the reaction was complete in 45 h when the initial excess
reagent was reduced to a 24-fold mole ratio relative to (TBA)2-
1.
8
9
3-methyl-1-butyl 2/1-(bromomethyl)butane
4-fluorobenzyl
1/4-fluorobenzyl bromide
2/4-fluorobenzyl chloride
2/methyl tosylate
5 d/reflux
59
1 h/150 °C 68
2 h/150 °C 50
4 h/150 °C 60
10 methyl
11 3-fluorobenzyl
2/3-fluorobenzyl chloride
12 4-chlorobenzyl 2/4-chlorobenzyl chloride 5 h/150 °C 75
13 4-bromobenzyl 2/4-bromobenzyl bromide 5 h/150 °C 70
14 3-bromobenzyl 2/3-bromobenzyl bromide 5 h/150 °C 65
15 4-methylbenzyl 2/4-methylbenzyl chloride 5 h/150 °C 55
16 4-methoxybenzyl 2/4-methoxybenzyl chloride 1 h/150 °C 30
a Acetonitrile was used in all reactions. b Isolated yield of B12(OR)12
based on (TBA)2-1.
Table 2. Selected Bond Lengths (Å) of 2, 3a, 3b, 9, 12, and 13
Based on Figure 5
closomer
BA
−OA
BB
−OB
CA
−OA
CB
−OB
BA
−BA
BB−BB
2
1.369(2) 1.398(2) 1.440(2) 1.433(2) 1.808(2) 1.862(2)
1.377(2) 1.403(2) 1.442(2) 1.437(2) 1.911(2) 1.862(2)
1.378(2) 1.404(2) 1.446(2) 1.441(2) 1.918(2) 1.864(2)
1.394(2) 1.384(2) 1.431(2) 1.858(3) 1.858(3) 1.864(2)
1.389(3) 1.388(2) 1.432(2) 1.860(3) 1.860(3) 1.867(2)
1.391(2) 1.388(2) 1.433(2) 1.869(3) 1.869(3) 1.868(2)
1.354(4) 1.388(2) 1.431(2) 1.914(5) 1.914(5) 1.866(2)
1.867(2)
3a
3b
9
12
1.375(3) 1.365(4) 1.408(3) 1.748(4) 1.748(4) 1.755(4)
1.386(3) 1.377(3) 1.417(3) 1.851(4) 1.851(4) 1.848(4)
1.389(3) 1.401(4) 1.437(3) 1.898(4) 1.898(4) 1.873(4)
1.364(6) 1.365(4) 1.409(6) 1.768(7) 1.768(7) 1.763(7)
1.383(6) 1.371(6) 1.415(6) 1.858(7) 1.858(7) 1.844(7)
1.387(6) 1.385(6) 1.437(6) 1.910(7) 1.910(7) 1.928(7)
Alternative precursors for the synthesis of the ether-linked
closomers are p-toluenesulfonate esters. Fortunately, for reac-
tions in which the desired organic halides are too volatile to be
conveniently handled (such as CH3Br) or the corresponding
alcohols are readily available, the corresponding p-toluene-
sulfonates can be utilized as convenient reagents. Thus, p-
toluenesulfonate esters have proven to be outstanding precursors
for closomer etherification reactions.
13
tetra-n-butylammonium]. The TBA salt of 1 was chosen due to
its enhanced solubility in such organic solvents as dichloro-
methane and acetonitrile, when compared with its alkali-metal
salt counterparts. Moreover, the traditional use of K2CO3 as a
base in the synthesis of polyether dendrimers40 is totally
ineffective here due to the extremely low solubility of the
potassium salt of 1 in organic solvents. Therefore, N,N-
diisopropylethylamine was employed as the base of choice for
closomer syntheses.
As previously reported,9 the reaction of (TBA)2-1 with excess
benzyl chloride and N,N-diisopropylethylamine in acetonitrile
solvent at the reflux temperature (method 1) produced structur-
ally characterized closomers having 12 benzyl ether groups and
the ability to undergo sequential redox reactions. In Table 1,
we report improved methods for the synthesis and purification
of a wide variety of alkyl and aralkyl ether closomers. An
alternative synthetic method (method 2) involved heating
reaction mixtures under moderate argon pressure in an autoclave
to attain elevated reaction temperatures, thereby drastically
reducing the time required for complete reaction when compared
to reactions carried out at the normal acetonitrile reflux
Oxidation of [closo-B12(OR)12]2-. In principle, the N,N-
diisopropylethylammonium ion byproduct generated during the
etherification reaction can compete with the tetrabutylammo-
nium ion as the counterion for the dianionic ether closomer
-
product. In addition, B12(OR)12 is generated during the
alkylation reaction through accidental oxygen contamination
(these closomers can be easily air oxidized to the anion radical)
and/or reaction with excess benzyl halide as shown in Scheme
2. Evidence of such radical formation is the observation of
bibenzyl in the mass spectrum of the crude reaction product.
These side reactions result in the formation of mixed salts and
oxidation states of the closomer ion which complicate product
isolation. To facilitate product isolation and purification, oxida-
tion of the crude reaction product to the uncharged hypercloso
closomer was followed by its purification using chromatography.
A variety of oxidants and reaction conditions were investi-
gated in the representative synthesis of dodeca(allyloxy)-
hypercloso-dodecaborane, such as O2, H2O2, Br2, I2, H2Cr2O7,
9
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Synthesis of Derivatives of hypercloso-B12H12
A R T I C L E S
Table 3. Distances (Å) between the Most Distant Antipodal Atom Pairs
closomer
antipodal
−outermost atom (on phenyl ring)
ligand bonded to BA
ligand bonded to BB
2
phenyl carbon-phenyl carbon
methyl carbon-methyl carbon
methyl carbon-methyl carbon
fluorine-fluorine
15.703(5), 15.728(4), 15.742(4)
10.487(4)
10.730(3)
15.858(5), 15.898(6), 15.927(5)
10.743(3)
10.597(3)
3a
3b
9
11
12
13
14
17.194(5)
18.486(3)
fluorine-fluorine
15.339(9), 17.501(7), 17.856(6)
19.496(3), 19.377(2), 19.572(3)
19.816(2), 19.696(2), 19.855(2)
14.402(2), 15.991(2), 18.255(2)
15.952(6), 16.955(5), 17.523(6)
17.850(2), 18.001(3), 18.162(2)
18.154(2), 18.434(2), 18.383(2)
17.791(2), 17.980(2), 18.128(2)
chlorine-chlorine
bromine-bromine
bromine-bromine
KMnO4, MnO2, HgCl2, Pd(OAc)2, PdCl2, Ag(NO3)2, Ag(OAc)2,
CuSO4, CuCl2, Fe2(SO4)3.nH2O, FeCl3, FeCl3‚6H2O, K3Fe(CN)6,
Fe(NO3)3, and tetrachloro-1,4-benzoquinone. As determined
from 11B NMR spectra, the best results were obtained with
Fe(III) in 90/5/5 ethanol/acetonitrile/H2O at room temperature.
The remaining oxidants (such as H2Cr2O7) either totally oxidized
the borane cage to boric acid or failed to react. A possible
explanation of these results is that the Lewis acidity of Fe(III)
facilitates the oxidation pathway by coordinating to the ether
oxygen centers via the nonbonding electron pairs.44,45 The
preparative yield of the neutral hypercloso compounds using
Fe(III) in 90/5/5 ethanol/acetonitrile//H2O generally ranged from
30% to 80% (yield of B12(OR)12 based on (TBA)21).
Figure 5 illustrates a common structural core of the dode-
caalkoxydodecaboranes consisting of the B12 framework and
the oxygen atoms R- and the carbon atoms â- to the boron
atoms. The variation of distance between the antipodal outermost
atoms shown in Table 3 is an indication of the nonspherical
nature of these closomers. This deviation from icosahedral
symmetry results in an approximate 3-fold axis as in 2, 11, 12,
and 13 and a true 3-fold axis as in 3a, 3b, and 9, while 14
exhibits no 3-fold axis. In a true icosahedron, all six distances
between these antipodal pairs of atoms would be equal.
All of the neutral 24-electron compounds exhibit desirable
properties, such as extreme solubility in common organic
solvents (e.g., hexane, benzene, dichloromethane, diethyl ether,
acetonitrile, and ethyl acetate), air stability over extended periods
of time, and thermal stability. In addition, the dodeca(allyloxy)
and dodeca(4-butenoxy) derivatives, 6 and 7, respectively, are
particularly interesting since they contain 12 terminal carbon-
carbon double bonds on the outer surface of the ether closomer,
offering the potential opportunity for further functionalization.
X-ray Diffraction Studies. The solid-state structures of 3
and 9 determined by X-ray diffraction are illustrated in Figures
3 and 4. An undistorted icosahedral hypercloso-[B12H12]
structure would have partially occupied, 4-fold degenerate
HOMOs, whose degeneracy can be removed by Jahn-Teller
distortion. Recently, a distorted icosahedron with D3d symmetry
was identified as an energy minimum in computations carried
out at the HF/6-31G(d) level for hypercloso-[B12H12] by
Fujimori and Kimura.15 However, McKee predicted by density
functional calculations that a Th structure has lower energy than
the observed D3d symmetry structure for 2 and 314 and concluded
that secondary effects, such as crystal packing, were responsible
for the disagreement. In fact, none of the seven neutral closomer
X-ray structures obtained showed evidence of Th symmetry.
The solid-state structures of 2, 3, 9, 11, 12, 13, and 14 have
been determined by X-ray crystallography, with 3 exhibiting
two types of symmetry, designated 3a and 3b. None of these
molecules are true icosahedra, but all show evidence of
crystallographic symmetry. Seven of eight types are centro-
symmetric, with the only exception being one of the two types
of 3, 3a, which contains only a 3-fold axis. The second type of
molecule in 3, 3b, has a 3-fold axis and a center of symmetry,
as does 9. The remaining structures have only a center of
symmetry. Selected bond distances for 2, 3a, 3b, 9, 12, and 13
are listed in Table 2.
Figure 5. A model of a dodecaalkoxydodecaborane with a 3-fold axis and
a center of symmetry.
Conclusions
Fifteen new dodecaalkoxy-hypercloso-dodecaborane deriva-
tives of [closo-B12(OH)12]2-, B12(OR)12, have been successfully
prepared and purified by employing sequential O-alkylation
followed by oxidation to the corresponding neutral hypercloso
derivative and gel filtration with silica or alumina. A variety of
alkyl and aralkyl halides, as well as p-toluenesulfonate esters,
were employed to produce the ether-linked closomers in
excellent yield. The closomer ether product, closo-[B12(OR)12]2-
,
is oxidized to hypercloso-[B12(OR)12]1-, which is further
oxidized with Fe(III) to hypercloso-B12(OR)12 followed by
isolation and characterization. Mass spectrometry and 1H, 13C,
19F, and 11B NMR spectroscopy were utilized to characterize
the hypercloso-B12(OR)12 species. The reduction of the neutral
species to the corresponding radical anion and subsequently to
the dianion was achieved using sodium borohydride in ethanol.
The described methodology also allows recovery of the un-
reacted aralkyl halide, alkyl halide, and p-toluenesulfonate
starting materials. An X-ray diffraction study of 3, 9, 11, 12,
(44) (a) Streitwieser, A. Chem. ReV. 1956, 56, 571. (b) Streitwieser, A. SolVolytic
Displacement Reactions; McGraw-Hill: New York, 1968. (c) King, J. F.;
Tsang, G. T. Y. J. Chem. Soc., Chem Commun. 1979, 1131.
(45) Ganem, B.; Small Jr., V. R. J. Org. Chem. 1974, 39, 3728.
9
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A R T I C L E S
Farha et al.
(TBA)2-1 and then progressing to an asymmetric peak which is
characteristic of partial random substitution of the vertexes during the
reaction. Final coalescence to a symmetrical singlet near -16 ppm
corresponds to [closo-B12(OR)12]2-, which is indicative of the comple-
tion of the reaction. The reaction mixture passed through different color
stages, starting with yellow and continuing with orange and finally
finishing as a light pink, dark purple, or blood red solution. When the
reaction was complete, the volatiles were removed using a rotary
evaporator. With the exception of 2, 6, 9, 11, 12, 13, 14, and 16, the
remaining residue was dissolved in dichloromethane and chromato-
graphed on neutral Al2O3 or silica. Yellow and pink/purple fractions
were separated, and the solvent was removed from both fractions using
a rotary evaporator. The 11B NMR spectra of both fractions were
obtained and revealed a resonance near 41 ppm corresponding to the
yellow fraction, which consisted of the neutral compound hypercloso-
B12(OR)12. The pink/purple fraction, which contained the charged
species, displayed a resonance near -15 ppm.
The pink/purple fraction or the residue of 2, 6, or 9 was dissolved
in 10.0 mL of 90/5/5 ethanol/acetonitrile/H2O, 2.00 g of FeCl3‚6H2O
was added, and the resulting solution was stirred for 12 h at room
temperature. The solvent was removed using a rotary evaporator. The
remaining brown residue was dissolved in dichloromethane and
chromatographed on neutral Al2O3 or silica. The yellow and pink/purple
fractions were separated. The above procedure can be repeated on the
recovered pink/purple fraction to accumulate additional hypercloso-
B12(OR)12.
General Procedure Method 2. After the starting materials were
mixed as described in method 1, the reaction mixture was then placed
into a 100 mL autoclave equipped with a glass liner under argon. The
reaction was carried out at 150 °C under elevated argon pressure until
reaction completion. The reaction was monitored via 11B NMR spectra,
as described above. When the reaction was complete, the procedure
described in method 1 was employed to isolate hypercloso-B12(OR)12.
Dodeca(benzyloxy)-hypercloso-dodecaborane (2). Method 1. The
reaction mixture was refluxed for 6 d after addition of 8.70 mL (73.0
mmol) of benzyl bromide. If the color of the reaction turns to yellow/
brown, the reaction should be repeated while oxygen is carefully
excluded. The excess benzyl bromide was removed chromatographically
by employing neutral alumina or silica. After elution with 35% EtOAc/
65% hexanes and then CH2Cl2 to remove the excess starting material,
the pink/purple product mixture was eluted with EtOAc. The purple
residue was oxidized according to the general procedures and then
chromatographed on silica by employing 35% EtOAc/65% hexanes to
elute a yellow fraction (2), and the remaining purple fraction was eluted
with EtOAc. The oily yellow 2 was crystallized from ethanol to give
the yellow-orange solid in 69% yield.
Method 2. After addition of 8.40 mL (73.0 mmol) of benzyl chloride,
the reaction was conducted at 150 °C and 800 psi for 4 h. When the
reaction was complete, the procedure described above for method 1
was followed. The neutral closomer 2 was isolated in 65% yield.
Compound 2 is an orange solid (melting point 147.5-149.0 °C).
1H NMR (500 MHz, CDCl3): δ 5.57 (s, 24 H), 7.02-7.28 (m, 60 H).
13C NMR (125.5 MHz, CDCl3): δ 73.1, 127.0, 128.1, 140.5. 11B NMR
(160 MHz, MeCN): δ 41.6. HRMS (MALDI): m/z calcd for
C84H84O12B12 (M-), 1415.7177; found, 1415.7247.
and 13 demonstrated that these neutral closomers have ap-
proximate D3d symmetry as does 2. All of the neutral closomers
exhibit a shortening of the B-O bond, indicating an increase
in double bond character as compared to a typical B-O single
bond. π-Back-bonding and steric factors, among others, may
be responsible for the stability of the hypercloso-B12(OR)12
species in these cases. The interesting oxidation-reduction
properties of these compounds will be presented in an upcoming
paper.13
Experimental Section
General Considerations. Both N,N-diisopropylethylamine and ac-
etonitrile were freshly distilled from CaH2 prior to use. All reactions
were carried out under anhydrous, oxygen-free conditions (oven-dried
glassware and argon). The organic halides and FeCl3‚6H2O were
purchased from Aldrich, Lancaster, and Fisher. Methyl and n-hexyl
p-toluenesulfonate were purchased from Acros Organics and TCI
America, respectively. All of the purchased chemicals were used without
further purification. 11B NMR spectroscopy (160 MHz) was performed
on a Bruker ARX-500 spectrometer and referenced externally to
.
BF3 Et2O. Bruker ARX-500, ARX-400, and Avance-500 spectrometers
were used to obtain 13C, 1H, and 19F spectra. Mass spectra were obtained
using a high-resolution Ultima 7T. The autoclave utilized in pressurized
reactions was an EZE-Seal manufactured by Autoclave Engineers, Inc.
Dicesium Dodecahydroxy-closo-dodecaborate (Cs2-1). In a 250
mL Erlenmeyer flask, 50.0 g (237 mmol) of CsCl was dissolved in
40.0 mL of ion-free water. In a separate 250 mL Erlenmeyer flask,
20.0 g (90.9 mmol) of [closo- K2B12H12] was dissolved in 50 mL of
ion-free water. The [closo- K2B12H12] solution was added slowly to
the CsCl solution with vigorous stirring. The resulting milky suspension
was chilled at -5 °C for 12 h. The white solid was separated by
filtration and then recrystallized from hot ion-free water. The white
crystals were separated by filtration, and the excess water was removed
by employing a lyophilizer. The total yield was 53.4 g (98%) of pure
Cs2[closo-B12H12].
The synthesis of Cs2[closo-B12(OH)12] from Cs2[closo-B12H12] was
performed as previously described.3,4 Precautions and careful planning
should always be employed to ensure the identity and purity of the
reagents. Adequate shielding is required to contain possible explosions.
Under no circumstances must hydrogen peroxide come in contact with
organic material or solVents due to the possibility of explosion.
Di(TBA)-dodecahydroxy-closo-dodecaborate [(TBA)2-1]. Ion-
exchange resin (Bio Rad AG 50W-X8) was used to convert Cs2-1 to
(TBA)2-1 as follows: In a 500 mL beaker, 200 mL of acid-form resin
was washed with ion-free water until a pH of 7.00 was obtained. With
stirring, 5 mL aliquots of 40% tetrabutylammonium hydroxide were
added until the suspension reached a pH greater than 10. The resin
was washed with ion-free water until neutral and then slurry-packed
in a column (5 × 30 cm). The column was wrapped with heating tape,
and the temperature was brought to 50 °C. A 10 g (16.7 mmol) portion
of Cs2-1 was dissolved in 1 L of boiling ion-free water. The solution
was then cooled to 50 °C and passed through the column, which was
then washed with an additional 1 L of warm water. The water was
removed using a rotary evaporator. The remaining traces of water were
removed azeotropically using benzene or simply lyophilized to yield
12.5 g (92%) of pure (TBA)2-1.
Alkylation of (TBA)2-1 Using Alkyl and Aralkyl Halides: Gen-
eral Procedure Method 1. Under an argon atmosphere, in a 100 mL
oven-dried Schlenk flask, 0.50 g (0.61 mmol) of (TBA)2-1 was
dissolved in 25.0 mL of freshly distilled acetonitrile. Employing a
syringe, 2.00 mL (11.5 mmol) of N,N-diisopropylethylamine and 76.0
mmol of alkyl halide or p-toluenesulfonate ester were added. The
reaction mixture was heated at the reflux temperature. The progress of
the etherification reactions was monitored using 11B NMR spectra,
starting as a symmetrical singlet near -18 ppm which corresponds to
Dodecaethoxy-hypercloso-dodecaborane (3). Method 2. In a 100
mL oven-dried Schlenk flask, 0.50 g (0.61 mmol) of (TBA)2-1 was
dissolved in 25.0 mL of freshly distilled CH3CN, and the solution was
chilled in an ice bath. Using a syringe, 2.00 mL (11.5 mmol) of N,N-
diisopropylethylamine and 16.6 mL (222 mmol) of bromoethane were
added. Under argon, the reaction mixture was transferred to a 100 mL
glass-lined autoclave via syringe. The reaction was carried out at 150
°C and 1000 psi. The reaction reached completion after 12 h. The 11
B
NMR spectrum of the completed reaction mixture showed two major
peaks, one around 38 ppm characteristic of 3 and the second near -16
ppm indicating charged closomers. A yellow fraction was eluted with
9
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Synthesis of Derivatives of hypercloso-B12H12
A R T I C L E S
1
CH2Cl2, and a purple fraction was eluted with EtOAc. Oxidation of
the purple fraction was performed as described in the general procedure.
The neutral closomer 3 was isolated in 70% yield.
Compound 3 is a dark-orange solid (sublimes at 168 °C, 1 atm). 1H
NMR (500 MHz, CDCl3): δ 1.22 (t, J ) 7.0 Hz, 36 H), 4.08 (q, J )
7.0 Hz, 24 H). 13C NMR (125.5 MHz, CDCl3): δ 17.7, 66.7. 11B NMR
(160 MHz, MeCN): δ 37.3. HRMS (MALDI): m/z calcd for
C24H60O12B12 (M-), 670.5292; found, 670.5279.
Compound 6 is a dark yellow-orange viscous oil. H NMR (500
MHz, C6D6): δ 4.94 (d, J ) 4.2 Hz, 24 H), 5.05 (dd, J ) 10.2, 1.80
Hz 12 H), 5.37 (dd, J ) 17.1,1.80 Hz, 12 H), 6.00 (m, 12 H). 13C
NMR (125.5 MHz, CDCl3): δ 71.5, 114.2, 136.9. 11B NMR (160 MHz,
MeCN): δ 41.0. HRMS (MALDI): m/z calcd for C36H60O12B12 (M-),
814.5298; found, 814.5304.
Dodeca(4-butenoxy)-hypercloso-dodecaborane (7). Method 1. The
reaction mixture was refluxed for 19 d after addition of 7.40 mL (73.0
mmol) of 4-bromo-1-butene. The excess 4-bromo-1-butene was re-
moved under high vacuum with warming at 50 °C. Following
completion of the reaction, the general oxidation procedure described
above was followed and the remaining residue was chromatographed
on neutral alumina. A yellow fraction corresponding to 7 was eluted
with 20% EtOAc/80% hexanes, and a pink/purple fraction was eluted
with EtOAc.The overall yield of the closomer 7 was 65%. Compound
7 should be stored at -20 °C or used immediately.
Dodeca(n-hexoxy)-hypercloso-dodecaborane (4). Method 1. After
addition of 9.00 mL (76.0 mmol) of 1-bromohexane, the reaction
mixture was refluxed for a total of 23 d under argon as described in
the general procedure. The 11B NMR spectrum of the reaction mixture,
starting from day 17, showed a small peak around 41 ppm characteristic
of the neutral closomer in addition to the -15 ppm singlet originating
from 42-. After completion of the reaction the excess 1-bromohexane
was removed using a high vacuum with warming at 60 °C. The
remaining red residue was chromatographed on neutral Al2O3 or silica.
A yellow fraction was eluted with 20% CH2Cl2/80% hexanes, and a
pink/purple fraction was eluted with EtOAc. Further oxidation of the
purple fraction was performed as described in the general procedure.
Closomer 4 was afforded in 80% yield.
Method 2. The reaction was conducted at 150 °C and 600 psi for 6
h. When the reaction was complete, the procedure described above for
method 1 was employed. The neutral closomer 7 was isolated in 62%
yield.
Compound 7 is a dark yellow-orange oil. 1H NMR (400 MHz,
CDCl3): δ 2.12 (dt, J ) 6.30, 4.06 Hz, 24 H), 4.09 (t, J ) 6.3 Hz 24
H), 4.93-5.02 (m, 24 H), 5.83 (dd, J ) 17.2, 1.60 Hz, 12 H), 5.81 (m,
Method 2. The reagents were combined as described in the general
procedure. The reaction was carried out at 150 °C and 500 psi for 8 h.
Isolation of 4 was performed as described above. The neutral closomer
4 was isolated in 75% yield.
12 H). 13C NMR (100.6 MHz, CDCl3): δ 36.6, 70.0, 115.8, 136.1. 11
B
NMR (160 MHz, MeCN): δ 41.4. HRMS (MALDI): m/z calcd for
C48H84O12B12 (M-), 982.7283; found, 982.7264.
1
The neutral closomer 4 is a dark yellow-orange oil. H NMR (400
MHz, CDCl3): δ 0.89 (t, J ) 7.1 Hz, 36 H), 1.32 (m, 72 H), 1.54 (m,
24 H), 4.02 (t, J ) 6.4 Hz, 24 H). 13C NMR (125.5 MHz, C6D6): δ
13.9, 22.8, 26.0, 31.8, 32.4, 70.5. 11B NMR (160 MHz, MeCN): δ
41.2. HRMS (MALDI): m/z calcd for C72H156O12B12 (M-), 1344.2811;
found, 1344.2834.
Dodeca(3-methylbutoxy)-hypercloso-dodecaborane (8). Method
2. After addition of 7.55 mL (72.0 mmol) of 1-bromo-3-methylbutane,
the reaction mixture was transferred by syringe into a 100 mL autoclave
vessel equipped with a glass liner. The alkylation reaction was carried
out at 150 °C and 1000 psi for 8 h. A yellow fraction was eluted with
benzene, and a red/pink fraction was eluted with EtOAc using silica.
Further oxidation of the red/pink fraction was performed as described
in the general procedure. The closomer 8 was afforded in 75% yield.
Dodeca(n-pentoxy)-hypercloso-dodecaborane (5). Method 1. After
addition of 9.20 mL (74.0 mmol) of 1-bromopentane, the reaction
mixture was refluxed for 21 d under argon. The 11B NMR spectrum,
starting from day 19, contained a small resonance near 41 ppm
associated with the neutral closomer. The excess 1-bromopentane was
removed using a high vacuum while the suspension was warmed to
50-60 °C. The remaining red residue was chromatographed on neutral
alumina or silica. A yellow fraction was eluted with 20% EtOAc/80%
hexanes, and a pink/purple fraction was eluted with EtOAc. Further
oxidation of the purple fraction was performed as described in the
general procedure. The overall yield of 5 was 78%.
Compound 8 is a dark-orange solid (sublimes at 185 °C, 1 atm). 1H
NMR (400 MHz, C6D6): δ 1.11 (d, J ) 6.67 Hz, 72 H), 1.81 (q, J )
6.67, 13.4 Hz, 24 H), 2.05 (m, 12 H), 4.57 (t, J ) 6.64 Hz, 24 H). 13
C
NMR (125.5 MHz, C6D6): δ 22.7, 25.1, 41.6, 69.1. 11B NMR (160
MHz, MeCN): δ 42.5. HRMS (MALDI): m/z calcd for C60H132O12B12
(M-), 1175.0946; found, 1175.0913.
Dodeca(4-fluorobenzyloxy)-hypercloso-dodecaborane (9). Method
1. This reaction should be carried out in the absence of light. After
addition of 9.00 mL (73.0 mmol) of 4-fluorobenzyl bromide, the
reaction mixture was refluxed for 5 d under argon. If the color of the
reaction becomes yellow/brown, it should be discarded and the system
should be checked for traces of oxygen and/or light. The excess
4-fluorobenzyl bromide was removed using chromatography (neutral
alumina) by employing 20% EtOAc/80% hexanes, and the pink/purple
product mixture was eluted with EtOAc. The purple residue was
oxidized according to the general procedures and then chromatographed
on silica by employing 20% EtOAc/80% hexanes to elute a yellow
fraction (9), and the remaining purple fraction was eluted with EtOAc.
The overall yield of the closomer was 59%. This compound should be
stored at -20 °C or used immediately.
Method 2. The reaction was conducted at 150 °C and 700 psi for 7
h. The reaction was monitored using 11B NMR. When the reaction was
complete, the workup procedure described above was employed. The
neutral closomer 5 was isolated in 75% yield.
1
Compound 5 was obtained as a dark yellow-orange oil. H NMR
(400 MHz, CDCl3): δ 0.89 (t, J ) 7.0 Hz, 36 H), 1.32 (m, 48 H), 1.55
(m, 24 H), 4.02 (t, J ) 6.4 Hz, 24 H). 13C NMR (125.5 MHz, CDCl3):
δ 14.0, 22.4, 28.3, 31.8, 70.1. 11B NMR (160 MHz, MeCN): δ 41.3.
HRMS (MALDI): m/z calcd forC60H132O12B12 (M-), 1175.1146; found,
1175.1160.
Dodeca(allyloxy)-hypercloso-dodecaborane (6). Method 1. After
addition of 6.40 mL (74.0 mmol) of allyl bromide, the reaction mixture
was refluxed for 7 d. The general procedure was followed to obtain 6.
If the reaction mixture becomes dark brown in color, the reaction should
be repeated. The product should be stored at -20 °C or used
immediately. The overall yield of 6 was 55%.
Method 2. The reaction was carried out at 150 °C and 550 psi for
1 h using 4-fluorobenzyl chloride. When the reaction was complete,
the purification procedure described in method 1, above, was followed.
The neutral closomer 9 was isolated in 68% yield.
1
Method 2. The reaction was conducted at 150 °C and 700 psi for 3
h using allyl chloride. The reaction was monitored using 11B NMR.
Following completion of the reaction, the general oxidation procedure
described above was followed and the remaining residue was chro-
matographed on neutral alumina. A yellow fraction corresponding to
6 was eluted with 20% EtOAc/80% hexanes, and a pink/purple fraction
was eluted with EtOAc. The overall yield of 6 was 60%.
Compound 9 is an orange solid (melting point 162-164 °C). H
NMR (400 MHz, CDCl3): δ 5.12 (s, 24 H), 6.88 (m, 24 H), 7.01 (m,
24 H). 13C NMR (100.6 MHz, CDCl3): δ 72.5, 115.1 (d, JC-F ) 21.6
Hz), 128.6 (d, JC-F ) 8.1 Hz), 135.7, 162.1 (d, JC-F ) 246.2 Hz). 11
B
NMR (160 MHz, MeCN): δ 41.7. 19F NMR (376.5 MHz, CDCl3): δ
-115.0. LRMS (MALDI): m/z calcd for C84H72B12O12F12 (M-),
1631.65; found, 1631.67.
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A R T I C L E S
Farha et al.
Dodeca(3-fluorobenzyloxy)-hypercloso-dodecaborane (11). Method
2. This reaction should be carried out in the absence of light. Following
the addition of 3.50 mL (30.0 mmol) of 3-fluorobenzyl chloride, the
reaction was carried out at 150 °C and 1500 psi for 4 h. The excess
3-fluorobenzyl chloride was removed using chromatography on silica
by employing benzene, and the purple product mixture was eluted with
acetonitrile.
chloride, the reaction was carried out at 150 °C and 1500 psi for 5 h.
The acetonitrile and unreacted base were removed using a rotary
evaporator. The yellow fraction was eluted with hexanes on silica. The
excess 4-methylbenzyl chloride was removed by employing benzene,
the purple product mixture was eluted with acetonitrile, and the solvent
was removed by employing a rotary evaporator. The oxidation of the
purple fraction was carried out as described for 11 to give a 55% yield.
Compound 15 is an orange/brown viscous oil. 1H NMR (500 MHz,
CDCl3): δ 2.31 (s, 36 H), 5.20 (s, 24 H), 6.96-6.99 (m, 48 H). 13C
NMR (125.7 MHz, CDCl3): δ 21.0, 72.7, 127.1, 128.5, 136.2, 137.7.
11B NMR (160 MHz, CH2Cl2): δ 43.0. MS (MALDI) m/z calcd for
C96H108O12B12 (M-), 1584.02; found, 1584.08.
A 0.50 g sample of the purple residue was dissolved in 15.0 mL of
95% ethanol, 1.00 g of FeCl3‚6H2O was added, and the resulting
solution was stirred for 12 h at room temperature. Solvent was removed
using a rotary evaporator. The remaining brown residue was dissolved
in dichloromethane and chromatographed on silica. A yellow fraction
(11) was eluted with dichloromethane, and the remaining pink/purple
fraction was eluted with EtOAc. The overall yield of the neutral
closomer was 60%.
Compound 11 is an orange solid (melting point 82.5-84.0 °C). 1H
NMR (500 MHz, CDCl3): δ 5.20 (s, 24 H), 6.79-6.94 (m, 36 H),
7.14-7.18 (m, 12 H). 13C NMR (100.6 MHz, CDCl3): δ 72.5, 113.4
(d, JC-F ) 21.8 Hz), 114.3 (d, JC-F ) 20.9 Hz), 122.0, 129.8 (d, JC-F
)8.0 Hz), 141.5 (d, JC-F ) 6.5 Hz), 162.1 (d, JC-F ) 244.9 Hz). 11B
NMR (160 MHz, CH2Cl2): δ 42.0. MS (MALDI): m/z calcd for
C84H72O12B12F12 (M-), 1631.65; found, 1631.72.
Dodeca(4-methoxybenzyloxy)-hypercloso-dodecaborane (16).
Method 2. If the color of the reaction becomes yellow/brown, the
reaction should be repeated. Following the addition of 3.50 mL (25.8
mmol) of 4-methoxybenzyl chloride, the reaction was carried out at
150 °C and 1500 psi for 1 h. The acetonitrile and unreacted base were
removed using a rotary evaporator. The excess 4-methoxybenzyl
chloride was removed by employing hexanes on silica. The yellow
fraction was eluted with 30% diethyl ether/70% chloroform, the purple
product mixture was eluted with acetonitrile, and the solvent was
removed by employing a rotary evaporator.
Dodeca(4-chlorobenzyloxy)-hypercloso-dodecaborane (12). Method
2. This reaction should be carried out in the absence of light. After
the addition of 5.90 g (36.0 mmol) of 4-chlorobenzyl chloride, the
reaction was carried out at 150 °C and 1500 psi for 5 h. The excess
4-chlorobenzyl chloride was removed using chromatography on silica
by employing benzene, and the purple product mixture was eluted with
acetonitrile.
A 0.50 g sample of the purple residue was dissolved in 15.0 mL of
95% ethanol, 1.00 g of FeCl3‚6H2O was added, and the resulting
solution was stirred for 12 h at room temperature. Purification of 12
was accomplished by following the procedure described above for 11
to give a 75% yield.
Compound 12 is an orange solid (melting point 158.5-160.0 °C).
1H NMR (500 MHz, CDCl3): δ 5.10 (s, 24H), 6.93 (d, J ) 7.72 Hz,
24H), 7.17 (d, J ) 7.88 Hz, 24H). 13C NMR (125.7 MHz, CDCl3): δ
72.4, 128.0, 128.5, 133.4, 137.9. 11B NMR (160 MHz, CH2Cl2): δ
42.8. MS (MALDI): m/z calcd for C84H72O12B12Cl12 (M-), 1828.91;
found, 1828.94
Dodeca(4-bromobenzyloxy)-hypercloso-dodecaborane (13). Method
2. This reaction should be carried out in the absence of light. After
the addition of 4.60 g (18.3 mmol) of 4-bromobenzyl bromide, the
reaction was carried out at 150 °C and 1500 psi for 5 h. The neutral
form of 13 was obtained by following the procedure described for 11.
The overall yield of 13 was 70%.
Compound 13 is an orange solid (melting point 165.0-165.5 °C).
1H NMR (500 MHz, CDCl3): δ 5.11 (s, 24 H), 6.89 (d, J ) 8.23 Hz,
24 H), 7.37 (d, J ) 6.72 Hz, 24 H). 13C NMR (125.7 MHz, CDCl3):
δ 72.4, 121.5, 128.3, 131.4, 138.4. 11B NMR (160 MHz, CH2Cl2): δ
42.2. MS (MALDI): m/z calcd for C84H72O12B12Br12 (M-), 2360.99;
found, 2360.98
Dodeca(3-bromobenzyloxy)-hypercloso-dodecaborane (14). Method
2. This reaction should be carried out in the absence of light. After
3.50 g (14.3 mmol) of 3-bromobenzyl bromide was added to the reaction
mixture, the reaction was carried out at 150 °C and 1500 psi for 5 h.
Purification and oxidation of 14 was carried out as described for 11.
The closomer was afforded in 65% yield.
Compound 14 is an orange solid (melting point 111.0-112.0 °C).
1H NMR (500 MHz, CDCl3): δ 5.20 (s, 24 H), 7.02-7.13 (m, 24 H),
7.33-7.39 (m, 24 H). 13C NMR (125.7 MHz, CDCl3): δ 72.4, 122.5,
125.0, 129.5, 130.0, 130.6, 141.6. 11B NMR (160 MHz, CH2Cl2): δ
42.3. MS (MALDI): m/z calcd for C84H72O12B12Br12 (M-), 2360.99;
found, 2360.94.
The purple residue (0.5 g) was dissolved in 15.0 mL of 95% ethanol,
1.00 g of FeCl3‚6H2O was added, and the resulting solution was stirred
for 1 h at room temperature. Solvent was removed using a rotary
evaporator. The remaining brown residue was dissolved in dichloro-
methane and chromatographed on silica. A yellow fraction (16) was
eluted with 30% diethyl ether/70% chloroform, and the remaining pink/
purple fraction was eluted with EtOAc. The overall yield of the
closomer was 30%.
Compound 16 is an orange/brown viscous oil. 1H NMR (500 MHz,
CDCl3): δ 3.73 (s, 36 H), 4.38 (s, 24 H), 6.80 (d, J ) 8.40 Hz, 24 H),
7.19 (d, J ) 8.40 Hz, 24 H). 13C NMR (100.6 MHz, CDCl3): δ 55.3,
71.5, 113.8, 129.4, 130.5, 159.2. 11B NMR (160 MHz, CH2Cl2): δ
42.7. MS (MALDI): m/z calcd for C96H108O24B12 (M-), 1775.19; found,
1775.2.
Alkylation of (TBA)2-1 Using p-Toluenesulfonic Acid Esters:
Dodeca(n-hexoxy)-hypercloso-dodecaborane (4). Method 2. In a 100
mL oven-dried Schlenk flask, 0.250 g (0.31 mmol) of (TBA)2-1 was
dissolved in 15.0 mL of acetonitrile. Using a syringe, 1.00 mL (5.75
mmol) of N,N-diisopropylethylamine and 5.00 mL (22.0 mmol) of
n-hexyl tosylate were added. Under argon the reaction mixture was
placed into a 100 mL glass-lined autoclave vessel using a syringe. The
reaction was conducted at 150 °C and 1100 psi for 2 h. The reaction
mixture changed from yellow to purple during the reaction. Acetonitrile
and unreacted base were removed using a rotary evaporator. The excess
n-hexyl tosylate was removed using a high vacuum with warming at
70 °C. The oxidation and purification procedures were as described
above to give 4 in a 70% yield.
Dodecamethoxy-hypercloso-dodecaborane (10). Method 2. In a
100 mL oven-dried Schlenk flask, 0.250 g (0.31 mmol) of (TBA)2-1
was dissolved in 15.0 mL of acetonitrile. Using a syringe, 1.00 mL
(5.75 mmol) of N,N-diisopropylethylamine and 5.00 mL (37.0 mmol)
of methyl tosylate were added. Under argon, the reaction mixture was
placed into a 100 mL glass-lined autoclave vessel via syringe. The
reaction was run at 150 °C and 1300 psi for 2 h. The reaction mixture
passed through a series of different colors starting with yellow, then
light pink, and finally purple. The acetonitrile and unreacted base were
removed using a rotary evaporator. The excess methyl tosylate was
removed utilizing a high vacuum with warming at 80 °C. The
purification and oxidation procedures employed for 3 were followed
to give 10 in a 50% yield.
Compound 10 is a dark-orange solid (sublimes at 130 °C, 1 atm).
1H NMR (400 MHz, CDCl3): δ 3.87 (s, 36 H). 13C NMR (100.6 MHz,
CDCl3): δ 58.9. 11B NMR (160 MHz, MeCN): δ 37.5. HRMS
Dodeca(4-methylbenzyloxy)-hypercloso-dodecaborane (15). Method
2. After the addition of 3.50 mL (25.5 mmol) of 4-methylbenzyl
9
18250 J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005

Synthesis of Derivatives of hypercloso-B12H12
A R T I C L E S
(MALDI): m/z calcd for C12H36O12B12 (M-), 502.3407; found,
502.3418.
Dodeca(4-chlorobenzyloxy)-hypercloso-dodecaborane (12). A deep
red crystalline needle obtained from a benzene solution was mounted
on a thin glass fiber. Data were not corrected for absorption. The
molecule is centrosymmetric, and the unique part is 1/2.
Crystallographic Studies. All measurements were made on a Bruker
Smart 1000 diffractometer equipped with a Mo tube. Data for 2 and 3
were collected at 100 K, while data for the other compounds were
collected at 25 °C. Calculations were made using software furnished
by Bruker. The conditions of the data collection have been tabulated,
and atoms were located by direct methods. None of these molecules
crystallize with solvent.
Dodeca(4-bromobenzyloxy)-hypercloso-dodecaborane (13) and
Dodeca(3-bromobenzyloxy)-hypercloso-dodecaborane (14). A deep
red crystalline plate obtained from a toluene solution was mounted on
a thin glass fiber. Data were corrected for absorption. The molecule is
centrosymmetric, and the unique part is 1/2.
Dodecaethoxy-hypercloso-dodecaborane (3). A deep red paral-
lelepiped obtained from a CH3OH solution was mounted on a thin glass
fiber. Data were corrected for absorption. There are two crystallo-
graphically different types of molecules in the unit cell. In molecule A
the unique part is 1/6, and this molecule has a 3-fold axis and is also
centrosymmetric. The other two molecules in the unit cell each have a
3-fold axis, and they are related to each other by a center of symmetry.
The unique part of molecule B is 1/3.
Dodeca(4-fluorobenzyloxy)-hypercloso-dodecaborane (9). A deep
red crystalline cut needle obtained from a toluene solution was mounted
on a thin glass fiber. No absorption correction was applied to these
data. The molecule is centrosymmetric and has a 3-fold axis (the unique
part is 1/6).
Acknowledgment. We are grateful to the National Science
Foundation (NSF) (Grants CHE-9730006 and CHE-0111718)
and for the National Science Foundation-Graduate Research
Fellowship for O.K.F. and Equipment Grants CHE-9871332,
CHE-98713320, CHE-9610080, CHE-9808175, CHE-9974928,
and CHE-0078299. We thank U.S. Borax, Inc. for a generous
grant-in-aid, which greatly assisted this research.
Supporting Information Available: Experimental procedures
and 1H, 13C, and 11B NMR and mass spectra of all compounds
(PDF) and CIF files for compounds 3, 9, 11, 12, 13, and 14.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Dodeca(3-fluorobenzyloxy)-hypercloso-dodecaborane (11). A red
crystalline parallelepiped obtained from a toluene solution was mounted
on a thin glass fiber. Data were corrected for extinction, but not for
absorption. The molecule is centrosymmetric, and the unique part of
the molecule is 1/2.
JA0556373
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