Open-Flask Synthesis of Amine-Boranes via Tandem Amine-Ammonium Salt Equilibration-Metathesis

Article abstract of DOI:10.1021/acs.inorgchem.5b00572

An amine-ammonium salt equilibration-metathesis sequence provides high-purity amine-boranes in excellent yields from sodium borohydride in refluxing reagent-grade tetrahydrofuran in an open flask.

Full text of DOI:10.1021/acs.inorgchem.5b00572

Communication
pubs.acs.org/IC
Open-Flask Synthesis of Amine−Boranes via Tandem Amine−
Ammonium Salt Equilibration−Metathesis
P. Veeraraghavan Ramachandran* and Ameya S. Kulkarni
Herbert C. Brown Center for Borane Research, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, United
States
S
* Supporting Information
Additives such as 18-crown-6 have been used to catalyze the
reaction in Et2O.17 Another reported modification involves
addition of organic acids to prepare specific amine−boranes.18
With in situ AB synthesis, followed by transamination
(Scheme 2), being envisioned, 1 equiv each of SBH, ammonium
ABSTRACT: An amine−ammonium salt equilibration−
metathesis sequence provides high-purity amine−boranes
in excellent yields from sodium borohydride in refluxing
reagent-grade tetrahydrofuran in an open flask.
Scheme 2. Proposed in Situ AB Synthesis−Transamination
Sequence
he past decade has seen amine−boranes receive consid-
T
erable attention because of their potential as safe carriers of
hydrogen for energy storage.1 In addition to their traditional use
as borane carriers for exchange reactions,2 applications as
precursors to high-performance polymers via catalytic dehy-
drocoupling3 and as reagents for novel organic transformations4
have made them even more relevant. They have also gained
significance as reagents of choice for the syntheses of metal
nanoparticles5 and nucleic acid analogues6 and electroless
plating.7 Furthermore, amine−boranes and their derivatives
display a wide range of biological properties, such as antiviral,
antineoplastic, antiinflammatory activities, etc.8 Recently, we
reported on the prospect of amine−boranes as hypergolic
bipropellants with consistently low ignition delays.9 This finding
led us to the decades-old quest to replace toxic hydrazine and its
derivatives as hypergolic fuels for space and missile applica-
tions.10 To expand our study, the preparation of large quantities
of a variety of amine−boranes became a necessity.
sulfate, and N,N,N-triethylamine (TEA, 1a) were refluxed in 1 M
THF.19 All of SBH was consumed within 1 h, and we were
delighted to observe, by 11B NMR spectroscopy, the formation of
99% TEA−borane (TEAB, 2a) and 1% AB (Table 1, entry 1).
a
Table 1. Effect of the Temperature on the TEAB Synthesis
b
entry
time (h)
temperature (°C)
TEAB−AB ratio
1
2
3
4
5
6
7
8
1
4
reflux
reflux
rt
99:1
100:0
85:15
85:15
86:14
88:12
88:12
91:9
1
4
rt
24
1
rt
40
The repeated large-scale preparation of ammonia borane
(AB)11 to obtain multigram quantities of the corresponding
amine−boranes via transamination12 (Scheme 1) hampered
4
40
24
40
a
Reactions were performed using 5 mmol each of SBH, (NH4)2SO4,
b
and TEA in 5 mL of THF, open to air. On the basis of the 11B NMR
spectra of reaction aliquots.
Scheme 1. Transamination of AB12
Continued refluxing for an additional 3 h converted the traces of
AB to TEAB (Table 1, entry 2). Filtering off the solids and
removing the solvent provided 90% yield of pure 2a (11B, 1H, and
13C NMR and hydride analysis). Notably, no dehydrogenation
byproducts were observed even in the presence of mildly acidic
(NH4)2SO4.20
Unexpectedly, when the reaction was carried out in THF at
room temperature (rt; Scheme 3), all of SBH was consumed
within 1 h, with the concurrent evolution of 1 equiv of H2.
Spectroscopic analysis revealed the formation of a mixture of
TEAB and AB in a 17:3 ratio, which remained essentially
unchanged over the next 3 h (Table 1, entries 3 and 4),
progress. This prompted us to adopt or develop either a more
efficient AB synthesis or a direct synthesis of amine−boranes. We
opted for the latter approach. Unfortunately, the reported
metathesis of ammonium salts with sodium borohydride
(SBH)13 lacks generality because of the poor solubility of SBH
and alkylammonium salts in common ether solvents, such as
diethyl ether (Et2O) and tetrahydrofuran (THF).14 This is
circumvented by using either more reactive, but flammable
lithium borohydride15 or SBH in dimethoxyethane,16 adding to
the cost of the product. Also, the lack of commercial availability
of the necessary amine salts restricts its wide applicability.
Received: March 12, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.5b00572
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
requiring 4 days for completion (entry 13). The optimal
concentration for best yields and fast reaction (entry 10,
highlighted in boldface) is 1 M THF.
Scheme 3. Room Temperature Formation of a TEAB−AB
Mixture
Having standardized the conditions for TEAB synthesis, the
protocol was applied to a variety of 1°, 2°, and 3° alkylamines to
demonstrate its generality as well as to prepare all of the amine−
boranes necessary for our project.9 As can be seen from Table 3,
suggesting that the reaction could not have proceeded via the
formation of AB as envisioned in Scheme 2. The extremely slow
transamination of AB with TEA even after 24 h at rt (Table 1,
entry 5)21 formed the basis for this assumption. Monitoring the
reaction temperature inside the flask revealed negligible change,
thus negating its role in the reaction progress. The formation of
TEAB at rt (Scheme 3) can only be rationalized by invoking an
amine−ammonium salt equilibrium,22 followed by salt meta-
thesis of triethylammonium sulfate with SBH (Scheme 4). Under
a
Table 3. Synthesis of Amine−Boranes from SBH
Scheme 4. Tandem Amine−Ammonium Salt Equilibration−
Metathesis
reflux conditions, either the amine−salt exchange is facilitated or
any AB formed undergoes facile transamination12 with the
remaining TEA. Refluxing is essential because maintaining the
temperature at 40 °C23 resulted only in a 91:9 mixture of TEAB
and AB in 24 h (Table 1, entry 8). Extended refluxing does not
deteriorate TEAB (11B NMR spectroscopy).24
Several ammonium salts, such as ammonium chloride,
fluoride, formate, and carbonate, were then scanned for the
salt-exchange reaction under varying conditions. The results,
summarized in Table 2, show that ammonium chloride and
Table 2. Optimization of Conditions for the Preparation of
a
TEAB from SBH
b
entry
NH4X
NH4Cl
SBH−NH4X ratio
time (h)
8
yield (%)
1
1:2
1:1
1:2
1:1
1:2
1:1
1:1
2:1
1:1
2:1
2:1
2:1
2:1
87
67
c
2
NH4Cl
20
d
3
NH4F
4
2
4
3
6
97
d
4
NH4F
74
e
5
NH4OCOH
NH4OCOH
(NH4)2CO3
(NH4)2CO3
(NH4)2SO4
(NH4)2SO4
(NH4)2SO4
(NH4)2SO4
(NH4)2SO4
110
e
6
71
7
78
53
90
90
85
92
88
c
8
20
9
4
a
Reactions were performed using 5 mmol of SBH, 2.5 mmol of
10
11
12
13
6
(NH4)2SO4, and 5 mmol of amine/2.5 mmol of diamine in 5 mL of
f
4
b
c
THF under reflux, open to air. Isolated yield. See the Supporting
g
d
16
Information. A mixture of diastereomers.
h
96
a
Reactions were performed using 5 mmol each of SBH and TEA in 5
most alkylamines gave excellent yields of the corresponding
amine−boranes (2a−2f, entries 1−6). Because of the distinct
advantages of diamine−bisboranes as potential hybrid rocket
fuels,25 1°, 2°, and 3° diamines were included in our study and
the corresponding bisboranes were isolated in high yields (2g−
2i, entries 7−9). Extensive application for reductive amination4j
prompted the inclusion of heteroarylamines, such as pyridine
(1j) and 2-picoline (1k), yielding the corresponding borane
adducts (2j and 2k, respectively, entries 10 and 11) in near-
quantitative yields.
b
c
mL of THF under reflux, open to air. Isolated yield. Peaks
corresponding to trace quantities of SBH were present in the 11B
d
e
NMR spectrum. 96% purity (11B NMR). Product contains a
f
g
triethylammonium formate impurity. 2 M reaction. 4 M reaction.
h
Reaction in Et2O.
sulfate provide the best outcomes (entries 1 and 9), with the
reaction with the latter being faster. Significantly, the reaction
stoichiometry revealed that, unlike for the AB synthesis where 2
equiv of ammonium ion were necessary,11a,b herein 1 equiv is
sufficient to achieve optimal yields, thus decreasing the overall cost
of the process. The reaction is extremely slow in refluxing Et2O,
In conclusion, we have developed an economical protocol to
prepare a variety of aliphatic and heteroarylamine−boranes in
excellent yields directly from SBH and the corresponding
B
DOI: 10.1021/acs.inorgchem.5b00572
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
(h) Vasilikogiannaki, E.; Titilas, I.; Vassilikogiannakis, G.; Stratakis, M.
Chem. Commun. 2015, 51, 2384. (i) Couturier, M.; Andresen, B. M.;
Tucker, J. L.; Dube, P.; Brenek, S. J.; Negri, J. T. Tetrahedron Lett. 2001,
42, 2763. Reductive Amination: (j) Matos, K.; Burkhardt, E. R.
Pharmaceutical Process Chemistry; Wiley-VCH Verlag GmbH & Co.
KGaA: Weinheim, Germany, 2010; p 127. (k) Ramachandran, P. V.;
Gagare, P. D.; Sakavuyi, K.; Clark, P. Tetrahedron Lett. 2010, 51, 3167.
Borenium Chemistry: (l) De Vries, T. S.; Prokofjevs, A.; Vedejs, E.
Chem. Rev. 2012, 112, 4246. B−H Insertion: (m) Cheng, Q.-Q.; Zhu,
S.-F.; Zhang, Y.-Z.; Xie, X.-L.; Zhou, Q.-L. J. Am. Chem. Soc. 2013, 135,
14094. (n) Chen, D.; Zhang, X.; Qi, W.-Y.; Xu, B.; Xu, M.-H. J. Am.
Chem. Soc. 2015, 137, 5268.
(5) (a) Kalidindi, S. B.; Sanyal, U.; Jagirdar, B. R. ChemSusChem 2011,
4, 317. (b) Lidor-Shalev, O.; Zitoun, D. RSC Adv. 2014, 4, 63603.
(6) Sergueeva, Z. A.; Sergueev, D. S.; Shaw, B. R. Nucleosides,
Nucleotides Nucleic Acids 2001, 20, 941.
(7) O’Sullivan, E. J. Fundamental and Practical Aspects of the
Electroless Deposition Reaction. In Advances in Electrochemical Science
and Engineering; Alkire, R. C., Kolb, D. M., Eds.; Wiley-VCH: New York,
2002; p 225.
amines. In addition to the wide substrate scope, the described
amine−ammonium salt equilibrium−metathesis protocol has
several significant benefits: (i) open-flask conditions; (ii) atom-
economical use of stoichiometric ammonium sulfate; (iii) use of
reagent-grade THF; (iv) no tedious purification required beyond
filtration; (v) recovery and recycling of the solvent over multiple
runs. The viability of this convenient preparation of amine−
boranes, demonstrated with a mole-scale synthesis of TEAB
(2a),26 should make them readily available and aid the
advancement of hydrogen energy and propellant research. In
addition, this could also find applications in the potential
synthesis of 1° amineborane-derived borazines.27
ASSOCIATED CONTENT
* Supporting Information
■
S
Representative procedures and characterization data for amine−
boranes. The Supporting Information is available free of charge
on the ACS Publications website at DOI: 10.1021/acs.inorg-
chem.5b00572.
(8) Burnham, B. S. Curr. Med. Chem. 2005, 12, 1995.
(9) Ramachandran, P. V.; Kulkarni, A. S.; Pfeil, M. A.; Dennis, J. D.;
Willits, J. D.; Heister, S. D.; Son, S. F.; Pourpoint, T. L. Chem.Eur. J.
2014, 20, 16869.
(10) (a) Clark, J. D. Ignition! An Informal History of Liquid Rocket
Propellants; Rutgers University Press: New Brunswick, NJ, 1972.
(b) Pichon, S.; Catoire, L.; Chaumeix, N.; Paillard, C. J. Propul. Power
2005, 21, 1057.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chandran@purdue.edu.
Notes
■
The authors declare no competing financial interest.
(11) (a) Ramachandran, P. V.; Gagare, P. D. Inorg. Chem. 2007, 46,
7810. (b) Ramachandran, P. V.; Mistry, H.; Kulkarni, A. S.; Gagare, P. D.
Dalton Trans. 2014, 43, 16580. (c) Heldebrant, D. J.; Karkamkar, A.;
Linehan, J. C.; Autrey, T. Energy Environ. Sci. 2008, 1, 156. (d) Chen, X.;
Bao, X.; Billet, B.; Shore, S. G.; Zhao, J.-C. Chem.Eur. J. 2012, 18,
11994.
ACKNOWLEDGMENTS
■
Financial assistance from the Herbert C. Brown Center for
Borane Research is gratefully acknowledged. A.S.K. is grateful for
a Purdue Research Foundation fellowship.
(12) AB is a superior alternative to the pyrophoric and moisture-
sensitive borane−methyl sulfide and borane−tetrahydrofuran.
Ramachandran, P. V.; Kulkarni, A. S. RSC Adv. 2014, 4, 26207.
(13) Noth, H.; Beyer, H. Chem. Ber. 1960, 93, 931.
DEDICATION
■
Dedicated to Professor Ei-ichi Negishi on the occasion of his
80th birthday.
(14) Andres, C.; Delgado, M.; Pedrosa, R. Synth. Commun. 1992, 22,
829.
REFERENCES
■
(15) Schaeffer, G.; Anderson, E. J. Am. Chem. Soc. 1949, 71, 2143.
(16) Kikugawa, Y. Chem. Pharm. Bull. 1987, 35, 4988.
(17) Kampel, V.; Warshawsky, A. J. Organomet. Chem. 1994, 469, 15.
(18) Kawase, Y.; Yamagishi, T.; Kutsuma, T.; Zhibao, H.; Yamamoto,
Y.; Kimura, T.; Nakata, T.; Kataoka, T.; Yokomatsu, T. Org. Process Res.
Dev. 2012, 16, 495.
(19) AB synthesis is carried out in 0.165 M THF. See ref 11a.
(20) AB decomposes in refluxing THF. Shaw, W. J.; Linehan, J. C.;
Szymczak, N. K.; Heldebrant, D. J.; Yonker, C.; Camaioni, D. M.; Baker,
R. T.; Autrey, T. Angew. Chem., Int. Ed. 2008, 47, 7493.
(21) Transamination at rt is only 5% complete in 20 h. See ref 12.
(22) Salt−base equilibrium has been described in the literature: Kar, R.
K.; Bera, S. C. J. Photochem. Photobiol. A: Chem. 1991, 56, 195.
(23) The reaction was attempted at 40 °C with prior knowledge of AB
synthesis at this temperature. See ref 11a.
(24) The stability of TEAB allows for its potential use in on-demand
AB production. Sutton, A. D.; Burrell, A. K.; Dixon, D. A.; Garner, E. B.;
Gordon, J. C.; Nakagawa, T.; Ott, K. C.; Robinson, P.; Vasiliu, M. Science
2011, 331, 1426.
(1) (a) Carre-Burritt, A. E.; Davis, B. L.; Rekken, B. D.; Mack, N.;
Semelsberger, T. A. Energy Environ. Sci. 2014, 7, 1653. (b) Muller, K.;
Stark, K.; Muller, B.; Arlt, W. Energy Fuels 2012, 26, 3691. (c) Mal, S. S.;
Stephens, F. H.; Baker, R. T. Chem. Commun. 2011, 47, 2922.
(d) Hamilton, C. W.; Baker, R. T.; Staubitz, A.; Manners, I. Chem. Soc.
Rev. 2009, 38, 279. (e) Staubitz, A.; Robertson, A. P. M.; Manners, I.
Chem. Rev. 2010, 110, 4079.
(2) (a) Baldwin, R. A.; Washburn, R. M. J. Org. Chem. 1961, 26, 3549.
(b) Cowley, A. H.; Mills, J. L. J. Am. Chem. Soc. 1969, 91, 2911.
(c) Budde, W. L.; Hawthorne, M. F. J. Am. Chem. Soc. 1971, 93, 3147.
(d) Brahmi, M. M.; Monot, J.; Desage-El Murr, M.; Curran, D. P.;
Fensterbank, L.; Lacote, E.; Malacria, M. J. Org. Chem. 2010, 75, 6983.
(e) Potter, R. G.; Camaioni, D. M.; Vasiliu, M.; Dixon, D. A. Inorg. Chem.
2010, 49, 10512.
(3) (a) Johnson, H. C.; Hooper, T. N.; Weller, A. S. Synthesis and
Application of Organoboron Compounds. In Topics in Organometallic
Chemistry; Fernandez, E., Whiting, A., Eds.; Springer: Berlin, 2015; Vol.
49, pp 153−220. (b) Vance, J. R.; Schafer, A.; Robertson, A. P. M.; Lee,
K.; Turner, J.; Whittell, G. R.; Manners, I. J. Am. Chem. Soc. 2014, 136,
3048 and references cited therein.
(4) Hydroboration: (a) Kanth, J. V. B. Aldrichimica Acta 2002, 35, 57.
(b) Scheideman, M.; Wang, G.; Vedejs, E. J. Am. Chem. Soc. 2008, 130,
8669. (c) Clay, J. M.; Vedejs, E. J. Am. Chem. Soc. 2005, 127, 5766.
(d) Johnson, H. C.; Torry-Harris, R.; Ortega, L.; Theron, R.; McIndoe, J.
S.; Weller, A. S. Catal. Sci. Technol. 2014, 4, 3486. Reduction and
Hydrogenation: (e) Hutchins, R. O.; Learn, K.; Nazer, B.; Pytlewski, D.;
Pelter, A. Org. Prep. Proced. Int. 1984, 16, 335. (f) Yang, X.; Zhao, L.; Fox,
T.; Wang, Z.-X.; Berke, H. Angew. Chem., Int. Ed. 2010, 49, 2058.
(g) Yang, X.; Fox, T.; Berke, H. Org. Biomol. Chem. 2012, 10, 852.
(25) Pfeil, M. A.; Dennis, J. D.; Son, S. F.; Heister, S. D.; Pourpoint, T.
L.; Ramachandran, P. V. J. Propul. Power 2015, 31, 365.
(26) Caution! Adequate safety precautions should be taken while carrying
out these experiments. Because of the toxic and corrosive nature of ammonia
and the liberation of large quantities of highly flammable hydrogen, the
reactions were carried out in a well-ventilated hood, with the reaction vessel
outlet directly leading into the hood exhaust.
(27) Wideman, T.; Sneddon, L. G. Inorg. Chem. 1995, 34, 1002.
C
DOI: 10.1021/acs.inorgchem.5b00572
Inorg. Chem. XXXX, XXX, XXX−XXX