Liquid-Phase Synthesis of Boron Isocyanates: Precursors to Boron Nanoparticles

Article abstract of DOI:10.1002/anie.201808352

The practical application of boron isocyanates has been hindered by their extremely high sensitivity and reactivity toward air and moisture. A convenient synthetic method in a suitable liquid media is reported for practical utilization of boron isocyanate

Full text of DOI:10.1002/anie.201808352

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Liquid-Phase Synthesis of Boron Isocyanates: Precursors to
Boron Nanoparticles
Authors: Yinghuai Zhu and Hosmane Narayan S
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201808352
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http://dx.doi.org/10.1002/ange.201808352

10.1002/anie.201808352
Angewandte Chemie International Edition
Liquid-Phase Synthesis of Boron Isocyanates: Precursors to Boron Nanoparticles
Yinghuai Zhua,*, Narayan S Hosmaneb,*
aSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine,
Macau University of Science & Technology, Avenida Wai Long, Taipa 999078, Macau
bDepartment of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois
60115-2862, USA.
E-mail: ZYH: yhzhu@must.edu.mo, NSH: hosmane@niu.edu
Abstract
The practical application of boron isocyanates has been hindered by their extremely high
sensitivity and reactivity toward air and moisture. A convenient synthetic method in a
suitable liquid media is reported for practical utilization of boron isocyanates. According to
NMR studies, the in situ generated boron isocyanates can be stored for at least one month
under an inert atmosphere at -20C without noticeable decomposition. The boron
tri(isocyanate) (B(NCO)3) has been converted to boron nanoparticles by reduction with
hydrogen under mild reaction conditions.
Keywords: boron isocyanates  metal cyanates  hydrogen reduction  boron nanoparticles 
polyurethanes
Isocyanates are esters of isocyanic acids, which contain the functional group –N=C=O. Wurtz
first reported a carbon-based organic isocyanate in 1849.[1] These compounds have wide
application both in commercial and consumer products due to their favorable qualities such
as relatively low molecular weights and high reactivity. Particularly, they are used as
monomers to manufacture polyurethanes.[2,3] Polyurethane compounds are widely used in
building, construction, transportation, furniture and bedding.[4] Organic isocyanates are also
useful reagents for the synthesis of urea and carbamate derivatives, which are starting
materials for the production of antidiabetic drugs and herbicides.[5-7] However, there are very
few reports in the past decades in terms of boron-based isocyanates due to their extremely
high air-sensitivity, especially for boron tri(isocyanate), B(NCO)3. The B(NCO)3 has been
synthesized by a gas-phase reaction process in a high vacuum of 0.1 Torr at about 100C,
with in situ analysis using HeI photoelectron spectra.[8,9] Theoretically, a synthetic method
used for carbon and silicon analogues could be used to prepare the boron-based isocyanates
1
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10.1002/anie.201808352
Angewandte Chemie International Edition
by treating a boron halide or an appropriate alkylboron halide with silver isocyanate in an
inert media, such as anhydrous benzene or toluene.[10,11] To overcome the disadvantages of
air-sensitivity, it is crucial to find a convenient and practical method to prepare and handle
boron isocyanates. Herein, we report an in situ synthesis and application of boron isocyanates
which makes it practical to handle these extremely high air and moisture-sensitive
compounds much more safely and conveniently. The resulting boron tri(isocyanate) was
found to be an effective reagent for the production of boron nanoparticles.
Carbon-based isocyanates can be prepared by the reactions of alkyl/aryl halides with alkali
cyanates (NaOCN, KOCN).[10] Therefore, we first investigated this reaction potential for the
synthesis of boron tri(isocyanate) (B(NCO)3) using an alkali metal cyanate (NaOCN, KOCN)
and boron trichloride (Equation 1). Since boron trichloride forms corrosive hydrogen chloride
upon exposure to moisture or alcohol, a toluene solution of boron trichloride (1.0 M in
toluene) was used in the procedure. Because BCl3 has also been reported to cleave C-O bonds
in ethers,[12,13] a relatively inert solvent, such as benzene or toluene, along with somewhat
polar solvent, acetonitrile (CH3CN), were used in the reaction. Unfortunately, the product
yields were extremely low, only a trace of B(NCO)3 was obtained from NaOCN and KOCN
salts as observed in the 11B-NMR spectra. When performed with silver isocyanate, the
reaction produced boron tri(isocyanate) in 85.4% yield based on ICP analysis (Equation 2).
…….. (Eq. 1)
…………………... (Eq. 2)
In the reaction between Ag(NCO) and BCl3 in benzene solution at 60-80C for 2 h, three
boron products, Cl2B(NCO), ClB(NCO)2 and B(NCO)3, were observed in the 11B-NMR
11
spectra. The B-NMR spectra showed chemical shifts at 46.4, 33.6, 22.9 and 13.7ppm for
1
BCl3, Cl2B(NCO), ClB(NCO)2 and B(NCO)3, respectively. The H and 13C-NMR spectra
displayed the typical toluene chemical shifts only. After heating at 100-105C for 1h,
followed by further heating at 115-125C for 5h, the reaction yielded an off-white product
mixture (Equation 2, see Figure S-1(a) in the Supporting Information). The B(NCO)3 was the
11
sole boron product in this reaction as evident in its B-NMR spectra in C6D6 solution (see
Figure 1 (a)). The product is essentially pure based on its NMR spectral data and, therefore, it
could be utilized in toluene solution. However, the isolation of highly air and moisture-
sensitive B(NCO)3 from the product mixture demands an extremely high vacuum of less than
0.1 Torr. [8,9]
The same reaction was also carried out in acetonitrile (CH3CN) as a solvent. As the reaction
temperature was raised gradually from room temperature to 125C, the reaction mixture
turned yellow (see Figure S-1 (b) in the Supporting Information). Consequently, four peaks
2
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10.1002/anie.201808352
Angewandte Chemie International Edition
were observed in 11B-NMR spectra (CD3CN), arising from BCl3, Cl2B(NCO), ClB(NCO)2
1
13
and B(NCO)3 at 0.9, 3.8, 7.8 and 10.5ppm, respectively. The H and C-NMR spectra also
displayed only typical toluene chemical shifts. However, the product composition did not
alter even after continuous heating of the solution to 115-125C for 5h based on its 11B-NMR
spectral analysis (see Figure S-2 in the Supporting Information). Although the exact reason
for this is unknown, but it can be assumed that the silver ion could undergo complexation
with CH3CN to form [Ag(NCCH3)2]+ which is of much lower reactivity than in benzene or
toluene. Nonetheless, this proposed side-reaction mechanism should be investigated
thoroughly in the near future.
Figure 1. The 11B-NMR spectra of reaction mixture of B(NCO)3 (a) and products of n-
BuBBr2, n-BuB(NCO)2, and PhB(NCO)2 (b) in C6D6.
n
The reaction of boron trichloride with tetrabutylammonium isocyanate, Bu4N[OCN], also
led to the formation of B(NCO)3 (see Figure S-3 in the Supporting Information). In this case,
both reagents are soluble in toluene and thus the reaction constitutes a homogeneous process.
The B(NCO)3 was obtained as a pure product based on 11B-NMR spectra after 5h at 115-
125C. The B(NCO)3 solution in toluene, obtained in this process, could also be conveniently
3
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10.1002/anie.201808352
Angewandte Chemie International Edition
transported and used for next steps, similar to the B(NCO)3 solution obtained from the
reaction between BCl3 and AgOCN.
Similarly, air-sensitive aryl boron isocyanate PhB(NCO)2 was synthesized by the reaction
between AgOCN and PhBCl2 in benzene solution at 105-110C over a period of 22h
11
(Equation 3). The B-NMR spectra showed the chemical shift at 29.6ppm for PhB(NCO)2.
11
The progress of the reaction was monitored by the B-NMR spectra (see Figure S-4 in the
Supporting Information). However, efforts in separating PhB(NCO)2 from the product
1
mixture was unsuccessful despite performing high vacuum distillation three times. The H
and 13C-NMR spectra displayed typical toluene and benzene chemical shifts, thus suggesting
the formation of a co-boiling liquid, probably an azeotrope of toluene and the product.
……..…(Equation 3)
n
n
An alkyl boron isocyanate, BuB(NCO)2, was synthesized by the reaction between BuBBr2
11
n
and AgOCN in anhydrous benzene (Equation 3). The B chemical shift () of BuB(NCO)2
has been shifted downfield when compared to that of Ph(NCO)2 and B(NCO)3 (see Figure 1
(b)) due to the steric bulk of the normal butyl group. The hydrolysis reactions of the boron
isocyanates were conducted in corresponding toluene solutions by carefully saturating with
moisture. The reactions yielded the corresponding boric acids. The 11B-NMR spectra showed
absorptions at  = 19.8, 32.9, and 37.3ppm for B(OH)3, BuB(OH)2 and PhB(OH)2,
respectively.
In the perspective of boron neutron capture therapy (BNCT) for cancer treatment, the
discovery of suitable boron delivery agents to tumors remains a big challenge.[14,15]
Utilization of boron nanoparticles could address the drug delivery issue in BNCT due to their
relatively large amount of boron in a tiny space. Among existing technology, the pyrolysis of
the decaborane (14) (B10H14) has been commonly utilized to produce the corresponding boron
nanoparticles.[16] In this process, a decaborane (14) cluster decomposes at a high temperature
of 700 to 900°C in an inert atmosphere. Alternatively, boron nanoparticles can also be made
by the reduction of boron tribromide with sodium metal at room temperature.[17] In the course
of the reduction process, the reactive bromine-functionalized boron nanoparticle
intermediates are formed which could further undergo a bromine replacement reaction to
generate the desired functional products. Nevertheless, both methods could be further
improved due to their inherent limitations, such as performing at an extremely high
temperature and utilization of corrosive reagents.
Here, we demonstrate the potential of these in situ generated boron isocyanates to produce
the desired boron nanoparticles by reduction with hydrogen. Accordingly, the reduction
process was carried out under a relatively mild reaction condition using hydrogen of 1atm at
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10.1002/anie.201808352
Angewandte Chemie International Edition
50C. The resulting boron nanoparticles (BNPs), isolated in the form of dark-brown powder,
were analyzed by NMR spectroscopy (in CDCl3) and transmission electron microscopy
(TEM). The 1H-NMR spectrum did not show any of the B-H peaks, but they were observed
when decaborane (14) was used as the precursor for the preparation of boron nanoparticles.
The TEM image (Figure 2 (a)) showed that the nanoparticles (NPs) have a relatively narrow
range of 10-50nm in particle size distribution. Solubility of boron nanoparticles in water,
diethyl ether and ethyl acetate were also investigated (Figure 2 (b)). The water solution was
found to be most stable and the NPs remained intact at least for three weeks. In contrast, the
solutions in ethyl acetate and diethyl ether were not stable and precipitation of BNPs was
observed after a few hours, with complete precipitation within one to two days.
(a)
(b)
Figure 2. The TEM image of boron nanoparticles (a) and the photos of BNP solutions (b).
In conclusion, the highly reactive and air-sensitive boron isocyanates can be prepared in situ
with high purity according to 11B-NMR spectral analysis. The solvated boron isocyanates are
relatively stable and thus could be handled conveniently. The solution of boron tri(isocyanate)
in toluene has been utilized as the precursor to prepare boron nanoparticles with narrow size
particle distribution. Investigation of further applications of the boron isocyanates and boron
nanoparticles are currently being carried out in our laboratories.
Experimental Section:
General procedure for boron isocyanate synthesis. In a dry/glove-box, the high-purity and
anhydrous AgOCN and anhydrous solvent (benzene or toluene) were taken into a two-necked
100-mL high-vacuum flask equipped with a stirring bar. The boron halide (BCl3 1.0M in
toluene, PhBCl2 97% and home-made BuBBr2 >97%) was then added carefully and the
5
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10.1002/anie.201808352
Angewandte Chemie International Edition
syringe was washed with the solution. An optimized ratio of molAgOCN/molBX3 of 4/1 was
used in all of the processes to obtain the best results under our optimized reaction conditions.
The flask was then removed from the glove-box and the reaction mixture in the flask was
heated to the desired temperature (>100C) in the dark with argon inlet (always keep the flask
cap tightly to avoid losing any product!). After completion of the reaction, the flask was
cooled to room temperature quickly before transferring it back to the glove-box.
Subsequently, the flask was stored in a refrigerator (-20C). The solid was precipitated and
filtered out to collect the clear solution product and kept in the refrigerator inside the glove-
box covering with aluminum foil for further investigation. The sample in anhydrous C6D6
was analyzed using air-sensitive NMR tubes (see Figures S2S4 in the Supporting
Information).
The boron nanoparticles were prepared by the reduction reaction of the above made B(NCO)3
in solution. A 5.0mL toluene solution of B(NCO)3 in a 100-mL high-vacuum flask equipped
with a stirring bar, was degassed three times and subsequently charged with highly pure
hydrogen gas to reach its pressure of 1atm. The reaction mixture was heated to 50C in the
dark for 30mins. After cooling to room temperature, the flask was transferred to the glove-
box, and the gases present in the flask were released carefully. The resulting dark-brown solid
was precipitated and collected by centrifuge, followed by washing with anhydrous toluene (2
x 5.0mL) before being collected and dried inside the glove-box. The boron nanoparticles
1
were analyzed by H and 11B-NMR spectra and by TEM (see Figures S5 and S6 in the
Supporting Information).
Acknowledgments
ZYH thanks the financial support from Faculty Research Grants (FRG-17-050-SP),
University of Science and Technology in Macau, and Tokyo Ohka Kogyo Co. Ltd. NSH
thanks Tokyo Ohka Kogyo Co. Ltd for their financial support, and Northern Illinois
University for the Board of Trustees Professorship.
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Angewandte Chemie International Edition
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