Fast colorimetric titration protocol for quantification of boron tribromide

Article abstract of DOI:10.1016/j.tetlet.2016.07.017

N,N-Dimethylaniline (DMA) was identified as a colorimetric titrant for accurate quantification of boron tribromide (BBr₃) solutions. The initial 1:1 DMA/BBr₃Lewis acid–base adduct formed upon addition of the first equivalent of BBr

Full text of DOI:10.1016/j.tetlet.2016.07.017

Accepted Manuscript
Fast colorimetric titration protocol for quantification of boron tribromide
Brianna N. Barbu, Talon M. Kosak, Amber J. Prins, Jason G. Gillmore, Andrew
L. Korich
PII:
S0040-4039(16)30839-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.07.017
TETL 47879
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
20 May 2016
30 June 2016
5 July 2016
Please cite this article as: Barbu, B.N., Kosak, T.M., Prins, A.J., Gillmore, J.G., Korich, A.L., Fast colorimetric
titration protocol for quantification of boron tribromide, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/
j.tetlet.2016.07.017
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Brianna N. Barbu, Talon M. Kosak, Amber J. Prins, Jason G. Gillmore, Andrew L. Korich

1
Tetrahedron Letters
Fast colorimetric titration protocol for quantification of boron tribromide
Brianna N. Barbua, Talon M. Kosakb, Amber J. Prinsa, Jason G. Gillmorea Andrew L. Korichb
aHope College, Department of Chemistry, 35 East 12th Street, Holland, MI 49422, United Sates
bGrand Valley State University, Department of Chemistry, 1 Campus Drive, Allendale MI 49401, United States
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
N,N-dimethylaniline (DMA) was identified as a colorimetric titrant for accurate quantification of
boron tribromide (BBr3) solutions. The initial 1:1 DMA:BBr3 Lewis acid-base adduct formed
upon addition of the first equivalent of BBr3 is bright blue in color. Addition of catalytic
quantities of BBr3 beyond the first equivalent initiates a instantaneously change the solution
from blue to yellow. This methodology will allow for accurate quantification of BBr3 so that
proper stoichiometric amounts of BBr3 may be used to facilitate a broad range of organic
transformations.
Available online
Keywords:
Titration
Boron Trihalide
Lewis Acid
Colorimetric Indicator
Boron
2009 Elsevier Ltd. All rights reserved.
———
 Jason G. Gillmore. Tel.: +1-616-395-7630; fax: +1-616-395-7118; e-mail: gillmore@hope.edu
 Andrew L. Korich Tel.: +1-616-331-8979; fax: +1-616-331-3230; e-mail: koricha@gvsu.edu

2
Tetrahedron
Titration of alkyl lithiums and other bases has been a common
approach.15 During the course of this work, we became
concerned over the quality and stability of our BBr3 solutions
over time. We also noticed significant color changes upon
addition of BBr3 to N,N-dimethylaniline which appeared to be
dependent on the stoichiometric ratio of the two reagents.
practice for many laboratories for more that a decade. As such,
numerous methodologies have been developed – including
colorimetric protocols – for fast, easy, and reliable quantification
in order to control precise stoichiometric addition of the
reagent.1–4 The same quantification techniques are not as
common for titrating Lewis acids. Often, Lewis acids (TiCl4,
AlCl3, BX3, etc.) are purchased as commercially available stock
solutions of “known” nominal concentration. Actual Lewis acid
concentration may be measured indirectly by first quenching the
reagent and titrating the resulting haloacid using chemical
indicator such as phenolphthalein and base.5 An alternative
approach uses EDTA, but metal complexation is difficult to
control and can give inconsistent results.6 Thus we believe a
direct visual colorimetric method to titrate Lewis acids that is fast
and easy to implement would be advantageous for many research
groups.
Recently, Blumberg and Martin reported a universal indicator
for titrating strong bases, hydrides, and Lewis acids.5 While the
authors report several commonly used Lewis acids, boron
tribromide (BBr3) was not listed in the report. A large number of
organic transformation rely on BBr3 as an initiator, catalyst, or
stoichiometric reagent.7–11 Correct stoichiometric addition can be
crucial to the overall success of such reactions. Furthermore,
BBr3 is known to degrade readily to produce HBr and boric
acid.12 As such, the aforementioned method for titrating Lewis
acids by degradation may provide erroneously high
concentrations since HBr may already be in solution due to
degradation of the BBr3 solution over time. If so, not all of the
HBr measured in the analysis would have come from hydrolysis
of BBr3 in the present analysis.
N,N-dimethylaniline in CH2Cl2 is nearly or completely
colorless and transparent (Scheme 2, left insert). Upon addition
of BBr3, the solution turns blue and deepens in color until a 1:1
stoichiometric balance is reached (Scheme 2, middle insert). UV-
visible spectroscopy shows a direct correlation between volume
of BBr3 solution added and the increase in absorbance at 613 nm
up to the equivalence point (see Supporting Information). We
attribute the blue color to the 1:1 complex of N,N-dimethylaniline
and BBr3 that is formed through a Lewis acid-base interaction
between nitrogen and boron center. The Lewis acid-base adduct
provides a stable zwitterionic complex, as evident by a district
signal in the 11B NMR at -3.9 ppm, similar to intermediates
observed by both Murakami and Ingleson.13,14 The strong B-N
interaction in the adduct does not allow for free BBr3 to be
present in solution and therefore only upon the addition of
catalytic quantities of BBr3 (beyond the first equivalent required
for adduct formation), does a reaction occur.14,16 Consequently,
an instant color change from blue to yellow occurs, providing a
clear visual endpoint to the titration (Scheme 2, right insert).
UV-vis spectroscopy at yellow endpoint of the titration indicates
1
the sudden disappearance of the 613 nm absorbance band. H
NMR characterization, after an aqueous workup, revealed a
mixture of products, presumably due to protodeborylation and
halodeborylation which are known to occur with electron-rich
arenes.17–19 While the resulting product mixture limits the
synthetic utility of this approach, the strong color changes
relating to the to stoichiometry of BBr3 to N,N-dimethylanline
makes for a powerful titration methodology.
Herein we report a fast colorimetric method for directly
titrating BBr3 solutions across a range of concentrations. Our
method relies not on producing hydrobromic acid but rather on
the Lewis acidity of the boron center of BBr3. It is widely
established that BX3 undergoes electrophilic aromatic
substitution upon activation of the boron trihalide with an amine.
Recently, Murakami and co-workers demonstrated that direct
borylation of 2-phenylpyridine proceeds through an initial Lewis
acid-base complex (Scheme 1a).13 EAS is facilitated by excess
BBr3 and an EtNi-Pr2. Along those lines, Ingleson and co-
workers have explored the borylation of N,N-dimethylaniline
derivatives by BCl3 with AlCl3 co-catalyst (Scheme 1b).14
Scheme 2. Progression of chemical and color changes over the
course of the titration of 1 M BBr3 with N,N-dimethylaniline.
In order to test the limits of this colorimetric titration, the
procedure was carried out using several different concentrations
of BBr3 ranging from 0.25 to 1.0 M as shown in Table 1. Each
stock solution was prepared in triplicate from a commercially
available 1 M solution in CH2Cl2. Each one of these solutions
was tested at least three times to ensure consistency and
reproducibility of this methodology. Across all concentrations
tested, the observed molarity by titration closely reflects the
expected molarity based on dilution. The intensity of the blue
color and the yellow endpoint decreased slightly as the BBr3
solution became more dilute but not so much as to hinder
effective colorimetric titration. Additionally, we titrated two
bottles of BBr3 that had been first opened three months prior to
testing and not particularly carefully stored. Not surprisingly, it
was found that the concentration of BBr3 in these solutions had
Scheme 1. Boron-based electrophiles for EAS reactions are
formed by an initial Lewis acid-base adduct between a
nitrogenous base and BX3.
Our interest in BBr3 stems from the Korich group’s
investigation of its mechanism for cleaving ethers and the
Gillmore group’s interest in attempting to extend this synthetic

3
decreased from the initial 1 M concentration to 0.33 M and 0.40
M respectively, due to degradation.
(2)
(3)
Dumhamel, L. J. Org. Chem. 1979, 44 (19), 3404–
3405.
Bowen, M. E.; Aavula, B. R.; Mash, E. A. J. Org
Chem. 2002, 67 (25), 9087–9088.
Table 1. Titrations of boron tribromide solutions in CH2Cl2.
Furthermore, testing of this methodology on a 1 M BBr3 solution
Entry Expected
Solution
Number
of trials
Observed
Molarity
Molarity
in heptane yielded identical results to those in CH2Cl2 (1.01 
0.04 M;
n
=
3).
Therefore, N,N-dimethylaniline in
1
2
1 M
Solution 1
Solution 2
Solution 3
Solution 1
Solution 2
Solution 3
Solution 1
Solution 2
Solution 3
Solution 1
Solution 2
Solution 3
n = 4
n = 6
n = 3
n = 3
n = 3
n = 3
n = 4
n = 3
n = 3
n = 5
n = 3
n = 3
0.99 0.07
1.01 0.07
0.95 0.03
0.75 0.02
0.74 0.01
0.76 0.03
0.48 0.07
0.48 0.04
0.46 0.02
0.25 0.05
0.26 0.07
0.25 0.02
dichloromethane proved to be a general and effective indicator
for determining the concentration of BBr3 solutions in both
halogenated and non-halogenated solvents. Further expanding
the scope of this methodology to other boron trihalides (X = Cl
and F) did not prove fruitful, presumably due to the lack of boron
electrophilic species formed at room temperature.14
3
4
0.75 M
0.50 M
0.25 M
5
In conclusion, we have shown that N,N-dimethylaniline in
dichloromethane is a simple and effective colorimetric indicator
for determining the concentration of BBr3 solutions in both
halogenated and non-halogenated solvents. Our method utilizes
the Lewis acidity of BBr3 directly to quantify a range of
concentrations. This direct approach allows for a more accurate
determination of concentration without the need for an external
catalyst. A dramatic color change from blue to yellow provides
an easily identifiable visual endpoint. The ability to quickly and
easily titrate commercial BBr3 solutions over time by this method
will enable more accurate stoichiometric addition of BBr3 to
laboratory reactions. This may also reduce waste in the
laboratory by allowing researchers to use older BBr3 solutions
more confidently if the degradation byproducts in the solution are
not themselves problematic.
6
7
8
9
10
11
12
(4)
(5)
(6)
(7)
(8)
(9)
Bergbreiter, D. E.; Pendergrass, E. J. Org. Chem.
1981, 46 (3), 219–220.
Blumberg, S.; Martin, S. F. Tetrahedron Lett. 2015,
56 (23), 3674–3678.
Yu, L.; Chen, D.; Li, J.; Wang, P. G. 1997, 62 (11),
3575–3581.
Qin, Y.; Cheng, G.; Sundararaman, A.; Jäkle, F. J.
Am. Chem. Soc. 2002, 124 (43), 12672–12673.
Dillon, E.; Dame, O. F. N. J. Am. Chem. Soc. 1942,
64 (5), 1128–1129.
General Procedures
1.0 M BBr3 in CH2Cl2 and N,N-dimethylaniline (≥99.5%
purity) were purchased from Sigma-Aldrich. Anhydrous CH2Cl2
was obtained from a solvent system. Additional concentrations of
BBr3 were prepared by adding the appropriate amount of 1.0 M
solution by syringe to an oven-dried septum-capped 10-mL
volumetric flask under inert (nitrogen or argon) atmosphere, and
diluting with anhydrous CH2Cl2. 1H and 11B NMR were taken on
a 300 MHz JEOL OXFORD spectrometer in CDCl3 that was
stored over 4 Å molecular sieves. 1H NMR spectra were
referenced to the deuterated solvent. 11B NMR were taken in a
Gao, P.; Portoghese, P. S. J. Org. Chem. 1996, 61 (7),
2466–2469.
(10) Zarate, C.; Manzano, R.; Martin, R. J. Am. Chem.
Soc. 2015, 137 (21), 6754–6757.
(11) Lawson, J. R.; Clark, E. R.; Cade, I. a.; Solomon, S.
a.; Ingleson, M. J. Angew. Chem. Int. Ed. 2013, 52
(29), 7518–7522.
.
quartz NMR tube and referenced to BF3 OEt2.
Titration Protocol
An oven-dried reaction flask was equipped with a magnetic stir
bar, placed under an inert atmosphere, and charged with N,N-
dimethylaniline (0.10 mL, 0.789 mmol) and anhydrous CH2Cl2
(1.5 mL). The BBr3 solution was added dropwise to the flask
using a gastight syringe. Initially, the solution turned increasingly
(12) McOmie, J. F. W.; West, D. E. Org. Synth. Coll. Vol
5. 1973, 412-413.
(13) Ishida, N.; Moriya, T.; Goya, T.; Murakami, M. J.
Org. Chem. 2010, 75 (24), 8709–8712.
(14) Bagutski, V.; Del Grosso, A.; Carrillo, J. A.; Cade, I.
a.; Helm, M. D.; Lawson, J. R.; Singleton, P. J.;
Solomon, S. a.; Marcelli, T.; Ingleson, M. J. J. Am.
Chem. Soc. 2013, 135 (1), 474–487.
blue prior to reaching a sudden yellow endpoint.
The
concentration of BBr3 solution was calculated from the volume
added, assuming a 1:1 molar ratio of BBr3 to N,N-dimethylamine.
(15) Kosak, T. M.; Conrad, H. A.; Korich, A. L.; Lord, R.
L. Eur. J. Org. Chem 2015, 34, 7460-7467..
(16) Del Grosso, A.; Singleton, P. J.; Muryn, C. A.;
Ingleson, M. J. Angew. Chem. Int. Ed. 2011, 50 (9),
2102–2106.
(17) Tramutola, F.; Chiummiento, L.; Funicello, M.;
Lupattelli, P. Tetrahedron Lett. 2015, 56 (9), 1122–
1123.
Acknowledgments
The Gillmore group gratefully acknowledges NSF CAREER
award CHE-0952768, the Dreyfus Foundation's Henry Dreyfus
Teacher-Scholar Program, and Hope College's Schaap Research
Fellows Program. The Korich group acknowledges Grand Valley
State University’s Office of Undergraduate Research
Scholarship and the Weldon Fund for financial support. We also
&
acknowledge helpful comments from an anonymous reviewer.
(18) Tale, R. H.; Toradmal, G. K.; Gopula, V. B.; Rodge,
A. H.; Pawar, R. P.; Patil, K. M. Tetrahedron Lett.
2015, 56 (21), 2699–2703.
References and notes
(19) Ahn, S.; Lee, C.; Kim, N.; Cheon, C. J. Org. Chem.
2014, 79 (16), 7277-7285.
(1)
Suffert, J. J. Org. Chem. 1989, 54 (30), 509–510.

4
Tetrahedron
Research Highlights



A simple and fast method for titrating boron
tribromide is presented.
Color changes are easily discernable allowing
for bench-top titration.
This method relies on the Lewis acidity of
boron tribromide and is able to quantify a broad
range of concentrations.