Communication pubs.acs.org/IC
Novel Convenient Synthesis of
10
B‑Enriched Sodium Borohydride
Alexander V. Safronov, Satish S. Jalisatgi, and M. Frederick Hawthorne* International Institute of Nano and Molecular Medicine, School of Medicine, University of MissouriColumbia, 1514 Research Park Drive, Columbia, Missouri 65211, United States S Supporting Information *
Scheme 1. Conventional Synthesis of 10B-Enriched Sodium Borohydride
ABSTRACT: A convenient and efficient synthesis of 10Benriched sodium borohydride [Na10BH4] from commercially available 10B-enriched boric acid [10B(OH)3] is described. The reaction sequence 10B(OH)3 → 10B(OnBu)3 → 10BH3·Et3N → Na10BH4 afforded the product in 60−80% yield. The reaction was successfully scaled to hundreds of gram per run.
S
odium borohydride is one of the most important products of the modern chemical industry. It is used in a number of commercial processes: paper production and bleaching, removing metals from wastewater streams, reduction of various industrial chemicals, and commercial production of drugs and vitamins.1 Sodium borohydride is also in demand for its important role in recent global hydrogen storage research.2 Although commercial sodium borohydride contains two natural isotopes of boron, 10B and 11B, it does not affect the reactivity because the hydride ion is the essential part of the molecule for many industrial applications. In some areas of research, however, the isotopic purity of boron compounds is very important. One of these areas is neutron detection in nuclear reactors and radioactive waste storages where isotopically enriched/pure 10B compounds can be used in neutron counters as an alternative to the scarce 3He isotope.3 Another area of research exploiting 10B-enriched materials is boron neutron capture therapy (BNCT), a binary cancer treatment method based on the reaction of a 10B nucleus with a thermal neutron. After selective delivery of the 10B-enriched therapeutic agent to the cancer cell followed by neutron irradiation, high linear energy-transfer particles (7Li3+ and 4 He2+) kill the cancer cell without affecting neighboring non-10B-containing healthy cells.4 Numerous 10B-enriched compounds were tested in BNCT, and the most efficient ones were found to belong to the family of polyhedral boron hydrides.5 Synthesis of the starting materials for BNCT such as [10B10H10]2− and [10B12H12]2− is usually achieved by pyrolysis of borohydrides-10B in alkane solvents.6 It should be mentioned that 10 B-enriched sodium borohydride is commercially unavailable. The conventional two-step synthesis of the enriched sodium borohydride includes (1) formation of a boronic ester via the reaction of 10B(OH)3 with an appropriate alcohol and (2) reaction of the boronic ester with NaH in mineral oil according to the Brown−Schlesinger procedure7 (Scheme 1). Trimethylborate-10B8 and tri-n-butylborate-10B6d,7 are the most commonly used boronic esters in this reaction. Both © XXXX American Chemical Society
esters react equally well with sodium hydride at 250−260 °C, resulting in a mineral oil suspension of the Na10BH4/sodium alkoxide mixture. Isolation of the target material is usually achieved by a combination of water treatment, extraction of the product by n-propyl- or isopropylamine, and its crystallization from diglyme. In a standard laboratory setting, this two-step procedure is convenient for the preparation of several grams of Na10BH4. However, the synthesis of 50−100 g batches of the product in standard laboratory glassware is problematic because of not only the high temperatures used but also the large amounts of highly alkaline byproducts suspended in the mineral oil produced. Because many research groups in the world develop new 10B compounds for BNCT applications in their in vitro and in vivo studies, a simple and efficient procedure for the variable-scale on-demand synthesis of Na10BH4 from the commercially available boric acid-10B is needed. The key purpose of this project was to make reaction conditions less harsh, which can be achieved by the gradual attachment of hydride ions to boron. The first step of the reaction sequence remained the same, and tri-n-butylborate-10B was chosen as the ester. The procedure6d was improved by omitting toluene from the reaction and using 1-butanol as both a reagent and an azeotropic water removal agent. Upon heating of the 10B(OH)3 (1; Scheme 2) solution in 1-butanol, the reaction components were distilled in the order water/1butanol azeotrope (bp 92−110 °C) → 1-butanol (bp 117 °C) → tri-n-butylborate-10B (2, bp 230−232 °C). However, because compound 2 is the highest boiling component of the reaction Scheme 2. Improved Synthesis of 10B(OnBu)3
Received: April 21, 2016
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DOI: 10.1021/acs.inorgchem.6b01002 Inorg. Chem. XXXX, XXX, XXX−XXX
Inorganic Chemistry
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mixture, after azeotropic removal of water and excess 1-butanol, the product 2 remaining in the distillation flask was pure enough to use without further distillation. Yields of 2 were close to quantitative (Scheme 2). The water/1-butanol mixture can further be separated using NaCl, and 1-butanol can be reused. In the next step, the ester 2 was reacted with lithium aluminum hydride9 in the presence of triethylamine in diethyl ether to produce triethylamine borane-10B (3; Scheme 3). The
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Fax: +1 (573) 882-6900. Notes
The authors declare no competing financial interest.
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REFERENCES
(1) Büchner, W.; Niederprünt, H. Pure Appl. Chem. 1977, 49, 733. (2) For example, see: (a) Mao, J.; Gregory, D. H. Energies 2015, 8, 430. (b) Yadav, M.; Xu, Q. Energy Environ. Sci. 2012, 5, 9698. (c) Santos, D. M. F.; Sequeira, C. A. C. Renewable Sustainable Energy Rev. 2011, 15, 3980. (d) Retnamma, R.; Novais, A. Q.; Rangel, C. M. Int. J. Hydrogen Energy 2011, 36, 9772. (e) Ç akanyıldırım, Ç .; Gürü, M. Int. J. Hydrogen Energy 2008, 33, 4634. (3) Neutron detectors. Alternatives to using helium-3. Technology Assessment, United States Government Accountability Office, Center for Science, Technology, and Engineering, GAO-11-753, www.gao.gov. (4) For example, see: Moss, R. L. Appl. Radiat. Isot. 2014, 88, 2. (5) For example, see: (a) Kueffer, P. J.; Maitz, C. A.; Khan, A. A.; Schuster, S. A.; Shlyakhtina, N. I.; Jalisatgi, S. S.; Brockman, J. D.; Nigg, D. W.; Hawthorne, M. F. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 6512. (b) Nakamura, H. Future Med. Chem. 2013, 5, 715. (6) (a) Hefferan, G. T. U.S. Patent 3,426,071, 1969. (b) Sayles, D. C. U.S. Patent 4,391,993, 1983. (c) Colombier, M.; Atchekzaï, J.; Mongeot, H. Inorg. Chim. Acta 1986, 115, 11. (d) Spielvogel, B.; Cook, K. U.S. Patent ApplicationUS2005/0169828A1, 2005. (7) (a) Schlesinger, H. I.; Brown, H. C.; Finholt, A. E. J. Am. Chem. Soc. 1953, 75, 205. (b) Adams, L.; Hosmane, S. N.; Eklund, J. E.; Wang, J.; Hosmane, N. S. J. Am. Chem. Soc. 2002, 124, 7292. (8) Schlesinger, H. I.; Brown, H. C.; Mayfield, D. L.; Gilbreath, J. R. J. Am. Chem. Soc. 1953, 75, 213. (9) (a) Hawthorne, M. F. J. Am. Chem. Soc. 1958, 80, 4291. (b) Hawthorne, M. F. J. Am. Chem. Soc. 1958, 80, 4293.
Scheme 3. Synthesis of 10BH3·Et3N
reaction proceeded at low temperature and was usually complete in 1 h after the addition of 2 (see the experimental details). Simple filtration and evaporation of the reaction mixture afforded pure 3 in 75−85% yield. It is important to note that triethylamine borane-10B is a liquid with a boiling point >200 °C; it is nonreactive toward water and oxygen. These properties make triethylamine borane-10B a very convenient intermediate product for the on-demand synthesis of Na10BH4. In the final step, compound 3 was reacted with NaH in a high-boiling alkane solvent (decalin or dodecane) to form sodium borohydride-10B (4; Scheme 4). The reaction was Scheme 4. Synthesis of Na10BH4
usually complete in 2 h and proceeded in yields close to quantitative. The reaction byproduct, triethylamine, was distilled off and collected for recycling in the previous step of the process. It should be mentioned that 3 was used in slight excess with respect to NaH to provide complete consumption of the latter. Compound 4 is insoluble in decalin or dodecane, and it was isolated by a simple filtration. The final step of the reaction sequence was successfully scaled up to produce 100− 150 g of Na10BH4 per run in standard glass laboratory equipment. In conclusion, a new convenient and efficient synthetic procedure for the variable-scale on-demand preparation of commercially unavailable 10B-enriched sodium borohydride was developed. The synthesis does not require extreme temperature conditions and can be performed in a standard laboratory setup on a scale from hundreds of milligrams to hundreds of grams in 60−80% total yield.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.6b01002. Experimental details, characterization, and NMR spectra of all prepared compounds (PDF) B
DOI: 10.1021/acs.inorgchem.6b01002 Inorg. Chem. XXXX, XXX, XXX−XXX
