A Study of Boratriazaroles: An Underdeveloped Class of Heterocycles

Article abstract of DOI:10.1021/acs.joc.6b01565

Boratriazaroles were discovered in the late 1960s, and since then, a variety of substituted boratriazarole derivatives have been prepared. However, no study has compared the properties of these BN heterocycles with their carbon-based analogues. In this work, we have prepared a series of boratriazarole derivatives and have investigated how structural variations in the five-member heterocycle affect photophysical and electronic properties. Boratriazaroles exhibit absorption and emission spectra comparable to those of their azacycle analogues but have a markedly lower quantum yield. The quantum yield can be increased with the incorporation of a 2-pyridyl substitution on the boratriazaroles, and the structural and optoelectronic properties are further influenced by the nature of the B-aryl substituent. Introducing an electron-deficient p-cyano group on the B-phenyl substituent creates a twisted intramolecular charge transfer state that causes a large Stokes shift and positive solvatochromism. Our work should serve to guide future synthetic efforts toward the application of boratriazaroles in materials science.

Full text of DOI:10.1021/acs.joc.6b01565

Subscriber access provided by Northern Illinois University
Article
A study of boratriazaroles – an underdeveloped class of heterocycles
Sean K Liew, Aleksandra Holownia, Andrew John Tilley,
Elisa I. Carrera, Dwight S. Seferos, and Andrei K Yudin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01565 • Publication Date (Web): 11 Aug 2016
Downloaded from http://pubs.acs.org on August 14, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
A study of boratriazaroles – an underdeveloped class of heterocycles
Sean K. Liew, Aleksandra Holownia, Andrew J. Tilley, Elisa I. Carrera, Dwight S. Seferos,*
Andrei K. Yudin*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Davenport and Lash Miller Chemical Laboratories, Department of Chemistry, University of
Toronto
80 St. George St, Toronto, Ontario M5S 3H6 Canada
Abstract
Boratriazaroles were discovered in the late 1960s, and since then, a variety of substituted
boratriazarole derivatives have been prepared. However, no study has compared the properties of
these BN heterocycles with their carbon-based analogues. In this work, we have prepared a series
of boratriazarole derivatives and have investigated how structural variations in the five-member
heterocycle affect photophysical and electronic properties. Boratriazaroles exhibit absorption and
emission spectra comparable to their azacycle analogues, but have a markedly lower quantum
yield. The quantum yield can be increased with the incorporation of a 2-pyridyl substitution on
the boratriazaroles, and the structural and optoelectronic properties are further influenced by the
nature of the B-aryl substituent. Introducing an electron-deficient p-cyano group on the B-phenyl
substituent creates a twisted intramolecular charge transfer state that causes a large Stokes shift
and positive solvatochromism. Our work should serve to guide future synthetic efforts towards
the application of boratriazaroles in materials science.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 33
1
2
3
4
TOC Figure:
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
ACS Paragon Plus Environment

Page 3 of 33
The Journal of Organic Chemistry
1
2
3
4
Introduction
5
6
7
8
The synthesis and study of boron-containing heterocycles has become an active area of
research.1,2 A common approach to incorporate boron into heterocycles is to substitute a C=C
functionality with the isosteric and isoelectronic B-N moiety.3,4 When B-N functionality is
incorporated into aromatic heterocycles, some degree of aromaticity is retained.5 The diversity of
new aromatic B-N containing heterocycles imparts new intermolecular interactions and changes
in photophysical properties, which can be exploited in areas such as optoelectronics6-8 and drug
discovery.9
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In 1926, Stock and Pohland reported the first example of interchanging C=C with B-N
with their synthesis of borazine, the BN analogue of benzene.10 Over the last decade, many
advances in the synthesis of new aromatic B-N containing heterocycles have been achieved.5-9,11-
13
Despite the vast amount of research dedicated to exploring the ramifications of C=C to B-N
28-
substitutions, 5-member aromatic boron-containing heterocycles,14-27 such as boratriazaroles,
37
have not been fully explored. Boratriazaroles are B-N isosteres of imidazoles and pyrazoles,
two azacycles that are important scaffolds in the pharmaceutical and agrochemical industry,38
and have various applications in materials science.39-43 The first documented boratriazarole
synthesis was by Paetzold, who reported only a 5% yield of the desired product.28 In 1971,
Dewar synthesized a number of boratriazaroles by treating a hydrazonamide with substituted
boronic acids.29,30 In 2015, Pitterna and co-workers investigated 3-pyridyl-containing
disubstituted boratriazaroles and found that the heterocycles were stable in slightly basic solution
that were in part attributed to steric bulk on the boronic acid substituent.31 Kinjo and co-workers
demonstrated the synthesis of new B-M and B-E boratriazarole complexes (M = metal, E = C-
based electrophile) derived from B-lithiated triazaboryl anions.32,33 Our lab explored new
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 33
1
2
3
4
5
6
7
8
9
boratriazarole-containing biaryl motifs derived from bromoacyl MIDA boronate scaffolds.34 The
resulting bis-heteroaryl products exhibited excellent thermal stability and formed intermolecular
hydrogen bonds in the solid state that are not possible with the C=C analogues. In spite of the
current interest in the synthesis and application of these heterocycles, no study has compared the
physical properties of boratriazaroles to their carbon-based analogues. Herein, we report the
synthesis, photophysical, and electronic properties of boratriazaroles and their analogues. Using
a range of experimental and computational techniques, we show how structural variations in the
five-member heterocycle and the aryl-substitution have a marked effect on the photophysical and
electronic properties of boratriazaroles. This work provides fundamental new insight into the
properties of boratriazaroles that will aid the design of new molecules and potential functional
materials.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Results
A family of trisubstituted azacycles were synthesized to investigate how varying the
arrangement of boron, nitrogen, and carbon atoms in the central five-member heterocycle affects
photophysical and electronic properties. The compounds of interest are trisubstituted
boratriazarole 1, triazole 2, pyrazole 3, and imidazoles 4 and 5 (Figure 1). Boratriazarole 1 is the
parent compound of interest. Triazole 2 is the analogue of 1 where NH-B is substituted by N=C.
Three other analogues, pyrazole 3, and imidazoles 4 and 5, are variants of 2 wherein each
nitrogen is systematically replaced with carbon (Figure 1).
4
ACS Paragon Plus Environment

Page 5 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ph
Ph
N N
NH-B
CC
N=C
Ph
N N
N
B
Ph
Ph
N
Ph
Ph
Ph
BN
H
boratriazarole 1
triazole 2
Ph
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
N N
N
Ph
Ph
Ph
pyrazole 3
Ph
Ph
N
N
H
NPh-imidazole 4
NH-imidazole 5
Figure 1: Analogues produced by NH-B to N=C and BN to CC swapping of boratriazarole 1.
Boratriazarole 1 was prepared from the hydrazone derived from benzaldehyde and phenyl
hydrazine (Scheme 1, Step a). The hydrazone was chlorinated using in situ generated N-
chlorosuccinimide dimethyl sulfide complex and the chloride was then displaced by ammonia to
afford the hydrazonamide (Steps b – c). After refluxing the hydrazonamide with phenyl boronic
acid, the crude product was purified by a short silica gel column followed by recrystallization in
a diethylether/hexanes mixture to furnish 1 in 50% yield (Step d). The four analogues of 1 were
prepared from commercially available starting materials following literature procedures (2 – 5,
Scheme 1). Briefly, the hydrazonoyl chloride precursor for 1 was also treated with benzylamine
and the resultant hydrazonamide was oxidized to furnish triazole 2 (Steps e – f).44 Pyrazole 3 was
prepared in one step by treating chalcone and phenylhydrazine with molecular iodine (Step g).45
NPh-imidazole 4 was prepared by a copper-mediated coupling of the corresponding amidine
with phenylacetylene (Step h).46 NH-midazole 5 was synthesized by the acid-mediated
condensation of benzil, benzaldehyde and ammonia (Step i).47
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 33
1
2
3
4
5
6
7
8
Ph
H
H
N
A)
N
O
a), b)
c)
d)
N N
N
Ph
N
Ph
B
Ph
Ph
Ph
H
N
H
Ph
NH2
Ph
Cl
1
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
e)
H
B)
Ph
Ph
3
O
N
g)
f)
2
H2N
Ph
N N
N
Ph
N N
N
N
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
N
H
Ph
Ph
Ph
C)
D)
Ph
H
O
Ph
NH
4
5
O
i)
h)
N
N
Ph
Ph
Ph
N
Ph
Ph
Ph
H
N
H
Ph
Ph
H
N
O
Scheme 1. Analogue syntheses. A) Synthesis of boratriazarole 1 and triazole 2 from a common
precursor; B) Synthesis of pyrazole 3; C) Synthesis of NPh-imidazole 4; D) Synthesis of NH-
imidazole 5. Conditions: a) PhNHNH2, EtOH, 80 ºC (52%); b) N-chlorosuccinimide (NCS),
SMe2, DCM, 0 ºC to -78 ºC to rt (64%); c) 7 N NH3 in MeOH, rt (99%); d) PhB(OH)2, toluene,
100 ºC (50%); e) BnNH2, TEA, MeCN (72%); f) Dess-Martin periodinane (DMP), DCM, rt
(62%);44 g) I2, 100 ºC (63%);45 h) CuCl2•H2O, pyridine, Na2CO3, O2, DCE, 70 ºC (30%);46 i)
NH4OAc, AcOH, 75 ºC (30%).47
Optical absorption experiments were conducted in chloroform solution at room
temperature to determine the photophysical properties of 1 – 5. The absorption spectrum of each
compound is generally broad and featureless. Boratriazarole 1 has an absorption maximum (λmax
)
at 283 nm, and a molar absorption coefficient of 2.12 × 104 M−1cm−1 (Figure 2, Table 1) In
comparison to its analogues, the absorption spectrum of 1 is increasingly more red-shifted
relative to NPh-imidazole 4, pyrazole 3, and triazole 2, while blue-shifted relative to NH-
imidazole 5. The red shift of 5 may be attributed to an increase in phenyl-phenyl conjugation
through the C-C double bond in the imidazole. Moreover, the absorption maximum of 1 is most
6
ACS Paragon Plus Environment

Page 7 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
similar to NPh-imidazole 4, differing by only 6 nm. Overall, the absorption maximum and the
molar absorption coefficient of boratriazarole 1 fall within the range of its carbon-swapped
analogues.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2: Normalized absorption and fluorescence emission spectra in chloroform for analogues
1 – 5. An excitation wavelength of 270 nm was used for 1 – 4, and 300 nm for 5.
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 33
1
2
3
4
5
Table 1: Summary of photophysical and computational data for analogues 1 – 5 ordered by
increasing λmax(abs)
.
6
7
8
9
Ph
Ph
Ph
Ph
Ph
2
3
4
1
5
Ph
N N
N
N N
N
N
N N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
B
Ph
Ph Ph
Ph
Ph
Ph
Ph
N
H
N
Ph
Ph
N
H
experimental data
λmax(abs) (nm)
λmax(em) (nm)
249
376
255
373
277
378
283
364
302
399
Stokes shift (cm-1)
13706
2.60
0.03
12406
3.09
0.12
9505
7863
2.12
0.01
8049
2.15
0.27
ε (× 104 M-1cm-1)
2.00
0.14
a
ΦF(rel)
computed data - B3LYP/6-311G++(d,p)//B3LYP/6-31G+(d,p)
268
265
298
311
339
λmax (nm)b
(0.307)
-7.26
-7.91
-7.71
(0.616)
(0.319)
(0.480)
(0.435)
-7.62
-6.93
-7.00
NICS (0)c
NICS (1)
NICS (-1)
-8.28
-7.87
-7.53
-7.98
-7.11
-7.27
-6.21
-5.06
-4.84
aQuantum yield calculated relative to PPO standard in cyclohexane ΦF = 0.84. TDDFT. λmax
b
corresponding to major oscillator; oscillator strength in parentheses. c GIAO method.
Using 2,5-diphenyloxazole (PPO) in cyclohexane as a standard (Φf = 0.84),48,49 we
determined the relative fluorescence quantum yield of compounds 1 – 5 in chloroform. We found
that NH imidazole 5 has the highest quantum yield of the series at 0.27,50 while the
boratriazarole 1 has the lowest quantum yield of 0.01 (Table 1, ΦF(rel)).25 The NH-B to N=C
swapped triazole 2 has a quantum yield of 0.03 and is most similar to 1. Although triazole 2 has
a low quantum yield, it exhibits the largest Stokes shift of 13706 cm-1, while boratriazarole 1 has
the smallest Stokes shift of 7863 cm-1 (Table 1).
8
ACS Paragon Plus Environment

Page 9 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In order to gain insight into the electronic properties of compounds 1 – 5, we performed
density functional theory (DFT) calculations using Gaussian 09.51 Time-dependent density
functional theory (TDDFT) calculations were carried out using B3LYP/6-311G++(d,p) on
geometries optimized using B3LYP/6-31G+(d,p). Stationary points were analyzed using
frequency calculations at 298 K. The calculations slightly over-estimated the absorption λmax
(corresponding to the transition with the highest oscillator strength), but were consistent with the
overall experimental trend (Table 1, λmax computed). We also performed nucleus independent
chemical shift (NICS) calculations at the centroid (0), and one Ångstrom above and below the
plane of the 5-member ring (NICS (1) and NICS (-1), respectively) to assess aromaticity.52 A
more negative NICS value implies higher aromatic character when comparing rings of the same
size. Based on the obtained values, boratriazarole 1 is in fact aromatic with a NICS (0) value of -
6.21, but to a lesser extent compared to 2 – 5 as indicated by their more negative NICS values
ranging from -8.28 to -7.26 (Table 1, NICS).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Having characterized boratriazarole 1 relative to analogues 2 – 5, we next sought to
understand how the B-aryl substituents of boratriazaroles influence the photophysical and
electronic properties. In our pursuit to synthesize boratriazaroles from various hydrazonamide
precursors, we found the preparation of 2-pyridyl hydrazonamides 6 to be the most efficient and
scalable. The attempted synthesis of various other hydrazonoyl chlorides using the chlorination
procedures led to no reaction due to insolubility in the case of 2-naphthyl substitution, or
mixtures of undesired products with 3- and 4-pyridyl substitution. We thus used 6 to prepare a
small series of 2-pyridyl-substituted boratriazaroles with various aryl boronic acids. The
appropriate B-aryl substituents were selected to investigate how electronic properties (7 – 12)
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 33
1
2
3
4
and steric strain (2,6-difluoro- 13, 14) influences structural and optoelectronic properties (Figure
5
6
3).
7
8
9
NHPh
NHR
Ph
R'B(OH)2
N
N N
N
N
B
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
toluene, 100 ºC
- 2 H2O
R'
N
R
7-16a
6a R = H
6b R = p-BrPh
Ph
N
B
Ph
N
B
Ph
Ph
N
B
N
N
N
N
N
B
N
N
N
OMe
Me
N
Cl
N
H
N
N
N
H
H
H
7 (42%)
8 (20%)
9 (51%)
10 (38%)
Ph
F
N
Ph
N
B
Ph
F
Ph
N
B
N
B
N
N
N
N
N
N
B
N
H
F
N
N
F
N
CN
F
N
H
N
H
11 (50%)
12 (63%)
13 (32%)
14 (63%)
Br
Figure 3: Boratriazarole synthesis using 2-pyridyl substituted hydrazonamides. aRecrystallization
yields after eluting through a plug of silica gel.
Recrystallization of four 2-pyridyl-substituted boratriazaroles yielded crystals suitable for
X-ray analysis. Electron-donating p-OMe-7 and withdrawing p-CN-12, as well as more sterically
encumbered 2,6-difluorophenyl boronic acid derived tri- and tetra- substituted boratriazaroles 13
and 14 were analyzed. A difference in the solid-state arrangement is observed for difluoro-
trisubstituted boratriazarole 13, which engages in two intermolecular hydrogen bonds with the
pyridine nitrogen and the NH of the central ring in a dimeric fashion. Interestingly,
crystallization of p-CN-12 led to crystals containing a 2:1 mixture of product to hydrazonamide
starting material. In the crystal, one molecule of 12 is hydrogen bonded to the hydrazonamide
with the same two atoms as that of 13, while the other molecule of 12 is not participating in any
hydrogen bonds (Figure 4).53 Compounds 7 and 14 do not participate in hydrogen bonding in the
10
ACS Paragon Plus Environment

Page 11 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
solid state. Table 2 lists pertinent structural bond lengths and dihedral angles (See Supporting
Information for additional X-ray crystallographic data).
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4: The unit cell of the crystal displaying two molecules of 12 and one molecule of
hydrazonamide 6a.
Table 2: Selected X-ray crystallographic data for 7, 12, 13, and 14.
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 33
1
2
3
4
5
6
7
8
ψ2
N Nb
Ph
R'
ψ3
ψ1
B
Na
ψ4
9
N
R
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
12a
13a
14
R = H, R' = p-OMe
R = H, R' = p-CN
1.427(2), 1.428(2)
1.432(2), 1.430(2)
6.77(11), 7.03(11)
54.73(5), 52.66(5)
11.20(10), 6.22(10)
--
R = H, R' = 2,6-F2
1.419(2), 1.416(2)
1.427(2), 1.434(2)
10.10(9), 13.02(9)
10.63(9), 13.66(9)
76.62(7), 51.58(7)
--
R = p-BrPh, R' = 2,6-F2
1.4300(17)
1.4312(17)
2.31(9)
72.03(4)
11.0(3)
--
1.438(3)
1.414(3)
32.05(13)
24.15(8)
56.43(9)
63.59(10)
B-Na (Å)
B-Nb (Å)
ψ1 (º)
ψ2 (º)
ψ3 (º)
ψ4 (º)
a
ψ = dihedral angle between the two aryl rings. Two values for 12 and 13 correspond to two
molecules in the unit cell.
Keeping the 2-pyridyl and N-phenyl groups on the boratriazarole constant allowed us to
assess the role of the B-aryl substituent on photophysical properties. To this end, we recorded the
optical absorption and fluorescence spectra for the six para-substituted boratriazaroles (7 – 12),
as well as the difluorophenyl boronic acid derived tri- and tetra-substituted boratriazaroles (13
and 14). The solution absorption maxima of compounds 7 – 13 fall between 301-308 nm, which
we assign to the 0 – 0 vibronic transition (Figure 5, Table 3, λmax). In contrast, tetrasubstituted 14
has an absorption maximum at 240 nm and a lower intensity band at 272 nm. Given the similar
energy of this longer wavelength transition to the 0 – 0 vibronic band of compounds 7 – 13, we
tentatively assign the feature at 272 nm to the 0 – 0 vibronic transition. The higher energy feature
at 240 nm thus presumably corresponds to a higher energy vibronic transition common to each
molecule in the series. All of the molecules have molar absorption coefficients ranging from
1.51 × 104 to 2.33 × 104 M-1cm-1 with 14 having the lowest (calculated at 272 nm) and p-CN-12
12
ACS Paragon Plus Environment

Page 13 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
having the highest value (Table 3, ε). The fluorescence emission λmax of all but one of the
compounds occurs within a small range from 368 to 377 nm (Figure 5, Table 3 λmax(em)). The
emission maximum of p-CN-12 occurs at 435 nm and exhibits the largest Stokes shift of 10015
cm-1. Tetrasubstituted 14 also has a large Stokes shift of 9664 cm-1. Furthermore, we obtained the
quantum yields for all compounds relative to 2,5-diphenyloxazole (PPO) and found that
switching the hydrazonamide-derived phenyl group of 1 to (2-pyridyl)-9 led to a drastic increase
in the quantum yield of the boratriazarole from 0.01 to 0.47 (Table 3, ΦF(rel)). The quantum yields
of the various trisubstituted compounds do not follow a trend based on the electronic properties
of the B-aryl ring (ΦF = 0.32 – 0.52). Tetrasubstituted boratriazarole 14 has a much lower
quantum yield of 0.13.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 5: Normalized absorption and fluorescence emission spectra in chloroform for
boratriazaroles 7 – 14. An excitation wavelength of 270 nm was used for 7 – 11, 13 – 14, and
300 nm for 10.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 33
1
2
3
4
5
6
Table 3: Summary of photophysical and computational data for boratriazaroles 7 – 14.
7
8
9
Ph
N N
R'
B
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
R
N
experimental
R = H
10
R = p-BrPh
7
8
9
11
12
13
14
R' = p-OMe R' = p-Me R' = p-H R' = p-Cl R' = p-F R' = p-CN R' = 2,6-F2 R' = 2,6-F2
λmax(abs) (nm)
λmax(em) (nm)
308
377
306
375
305
374
303
372
305
372
303
435
301
368
272
369
Stokes shift
(cm-1)a
5942
6013
6049
6122
5905
10015
6049
9664
ε (× 104 M-1cm-1)
1.99
0.52
2.06
0.44
1.77
0.47
2.21
0.32
2.05
0.52
2.33
0.32
2.11
0.51
1.51
0.13
b
ΦF(rel)
computed
B3LYP/6-311G++(d,p)//B3LYP/6-31G+(d,p)
335
(0.334)
329
(0.369)
327
324
(0.391)
324
(0.377)
318
(0.377)
321
(0.373)
311
(0.179)
λmax (nm)c
(0.377)
NICS (0)d
NICS (1)
NICS (-1)
-6.52
-5.25
-5.08
-6.59
-5.26
-5.15
-6.64
-5.37
-5.27
-6.69
-5.45
-5.20
-6.69
-5.36
-5.22
-6.78
-5.46
-5.30
-6.98
-5.56
-5.56
-6.74
-5.04
-5.27
a The Stokes shift is quoted as the difference between the 0 – 0 vibronic band of the solution
absorption spectrum, and the solution emission maximum. b Quantum yield calculated relative to
c
PPO standard in cyclohexane (ΦF = 0.84). TD-DFT. λmax corresponding to major oscillator;
oscillator strength in parentheses. d GIAO method.
Compounds with large Stokes shifts often exhibit solvatochromic behaviour.54-56 Since p-
CN-12 displayed a significantly larger Stokes shift relative to the other compounds in the series,
we investigated the solvatochromic behaviour of this compound by recording the absorption and
emission spectra of 12 in solvents with varying polarities. The absorption maximum of 12 varies
within a small range of 297 – 303 nm when recorded in these solvents (Table 4). The emission
maximum of 12, however, is substantially red-shifted as the polarity of the solvent increases. In
14
ACS Paragon Plus Environment

Page 15 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
diethylether, the emission maximum appears at 412 nm, corresponding to a Stokes shift of 8950
cm-1, while in the more polar acetonitrile, the emission maximum appears at 448 nm with a
correspondingly larger Stokes shift (11576 cm-1). Using methanol and DMSO as solvent led to
significant emission quenching compared to the other solvents, possibly due to sample
decomposition. Nevertheless, a Stokes shift of similar magnitude to that of acetonitrile was
observed for each of these polar solvents (see Supporting Information), and is consistent with
positive solvatochromism.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4: Absorption and emission maxima, and Stokes shift for 12 in different solvents.
Solvent
Et2O
301
THF
302
EtOAc
300
CHCl3
303
MeCN
295
λmax(abs) (nm)
λmax(em) (nm)
412
424
424
435
448
Stokes shift (cm-1)a
8950
9528
9748
10014
11576
a The Stokes shift is quoted as the difference between the 0 – 0 vibronic band of the solution
absorption spectrum, and the solution emission maximum.
We next conducted computational studies on the substituted boratriazarole to further
understand their electronic properties. As with the analogues 1 – 5, the calculated absorbance
maxima were slightly overestimated, but consistent with the trend of the experimental values for
7-14 (Table 3, λmax computed). NICS calculations revealed that the central boratriazarole ring is
relatively more aromatic with the 2-pyridyl substitution compared to 1. Consistent with the data
from the B-N bond lengths derived from the X-ray crystallographic data (vide infra), NICS
calculations also show a trend of increased aromaticity with more electron withdrawing
substituents. In order to gain insight into the substantial Stokes shift with p-CN-12, the HOMO
and LUMO orbitals from the TDDFT calculations were visualized. In general, p-OMe, p-Me, p-
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 33
1
2
3
4
5
6
7
8
9
H, p-Cl, p-F, and 2,6-difluoro substituted boratriazaroles have very similar HOMO and LUMO
orbitals (Figure 6, only OMe and Cl shown, see SI for more detail). The HOMO is delocalized
amongst the four aryl rings, while the LUMO predominates on the pyridyl ring with no
contribution from the B-aryl substituent. The introduction of the p-CN substitution drastically
alters the electronic distribution in the LUMO orbital, which predominates on the B-aryl
substituent. With the additional N-aryl ring in 14, there is less delocalization in the HOMO
orbital and a large contribution of the new N-aryl ring to the LUMO orbital. The transitions
corresponding to the highest oscillator strengths are from the HOMO to the LUMO for all
compounds except 12. While the HOMO to LUMO transition does contribute to the spectrum of
12 (f = 0.187), the transition with the highest oscillator strength is HOMO to LUMO+1 in nature
(f = 0.377). The electronic distribution in the LUMO+1 of 12 resembles that of the LUMOs of all
of the other compounds.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
16
ACS Paragon Plus Environment

Page 17 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
LUMO
LUMO+1
-1.803
-1
-2
-3
-4
-5
-6
-7
-1.561
-1.653
-1.678
-5.936
10
-2.093
-5.835
-6.058
-6.142
HOMO
7
12
14
Figure 6: The computed HOMO and LUMO orbitals of p-OMe-7, Cl-10, and CN-12, and 14.
Discussion
Based on our study, the boratriazaroles are less aromatic compared to the carbon-based
analogues. This property is elucidated by the NICS calculations, whereby the NICS values for 1
are less negative than those for 2 – 5. We conclude that the boratriazaroles do not exist as the
formally zwitterionic RHN+=B-NPh species; rather, the NH lone pair in 1 is more localized on
nitrogen and partially donating into the boron p-orbital. The overall aromaticity is further
supported by the X-ray crystallographic data of 7, 12, 13, and 14, which show that the central
boratriazarole rings are essentially planar with root mean square deviations in the range of 0.004
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 33
1
2
3
4
5
6
– 0.006 Å. The trend of decreased aromaticity in the boratriazaroles is consistent with other
studies of BN-heterocycles.26,27,57
7
8
9
We have investigated changes in the boron-nitrogen bond lengths, as well as changes in
the dihedral angles between the central ring and its flanking aryl groups (Table 2) in the X-ray
crystallographic data of the 2-pyridyl-boratriazarole analogues p-OMe-7, p-CN-12, 2,6-difluoro-
13, and tetrasubstituted-14. Since Nb is bound to a phenyl group, which will delocalize the
nitrogen lone pair, the resultant Nb-B bond lengths for 7, 12, and 13 are longer than Na-B. There
is more donation of the NaH lone pair into the p-orbital of boron. As the electron withdrawing
nature of the B-aryl substituent increases, the bond length between the boron and both nitrogen
atoms decreases. By swapping the NH with N-aryl (as in 14) the Nb-B bond becomes shorter
than Na-B, presumably due to steric repulsion between the Na-aryl group with the pyridyl and B-
aryl substituents. For each compound, all B-N bond lengths are longer than a B-N double bond
(ca. 1.41 Å) implying electron delocalization in the aromatic system.58
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Steric repulsion was also assessed by the dihedral angles between the central
boratriazarole ring and its flanking aryl rings. For 7 and 12, the Nb-phenyl ring (ψ2) is twisted the
most out of plane at 72º and ca. 53º, respectively, while the pyridyl (ψ1 < 7º) and B-aryl (ψ3 <
12º) are nearly in plane with the central ring. In contrast, bulkier difluoro-13 has the B-aryl group
twisted approximately 64º out of plane while the pyridyl and phenyl groups are more in plane
(ψ1,2 < 14 º). Once an aryl substituent is introduced on Na as with 14, all dihedral angles increase,
thus decreasing electronic communication among the π-systems and affecting the absorption
properties.
With the exception of the NH-imidazole 5, the boratriazaroles contain a hydrogen bond
donor NH that is absent from the other analogues. In our previous studies of boratriazaroles, we
18
ACS Paragon Plus Environment

Page 19 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
observed that the NH functionality is capable of engaging in intermolecular hydrogen bonding
interactions in the solid state.34 Hydrogen bonding capabilities were also further elucidated in the
solid state of the (2-pyridyl)-boratriazaroles. Only difluoro-13 was capable of participating in
intermolecular hydrogen bonding in a dimeric fashion. The other observed case of hydrogen
bonding was with p-CN-12, which was unable to pack in a dimeric fashion, but cocrystallized
with the hydrazonamide starting material (vide supra, Figure 4). Since the dihedral angle ψ3 of
13 is high (>50º) due to the difluoro substitution, the compound is able to accommodate
hydrogen-bond donor/acceptor interactions with a second molecule of 13 with minimal steric
penalty. On the other hand, ψ3 of 12 is much lower (<12º) with increased electronic
communication between the two aryl rings, which renders dimerization in the solid state
sterically inaccessible. The cocrystallized hydrazonamide can be oriented to minimize steric
repulsion and favourably hydrogen bond with the boratriazarole (See Supporting Information for
X-ray crystallographic data). The unusual cocrystallization of the product with residual starting
material may speak to the high propensity of these pyridyl boratriazaroles to participate in
hydrogen bonding, which is a desirable property for applications in medicinal chemistry.
Relative to the carbon-based analogues (2 – 5), boratriazarole 1 generally has similar
absorption and emission spectra, but has a very low quantum yield. The quantum yield, however,
can be increased with the inclusion of a pyridyl group in the molecule. A number of conclusions
can be drawn from the photophysical data, as well as the TD-DFT calculations and molecular
orbital diagrams for the HOMO and LUMO of 7 – 14. With trisubstituted boratriazaroles 7 – 13,
the HOMO is delocalized across the entire molecule. With exception of p-CN-12, the main
computed transition contributing to the absorption spectrum is a HOMO to LUMO π-π*
transition with some charge transfer character away from the B-aryl ring and onto the pyridyl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 33
1
2
3
4
5
6
7
8
9
ring. When donor and acceptor units are connected through a single bond, such charge-transfer
behavior is accompanied by a change in geometry to establish a lower-energy twisted
intramolecular charge-transfer state (TICT).59 This lower energy TICT state is observed in the
emission spectrum as a significant Stokes shift. The main computed transition in 12 also involves
similar charge-transfer behavior away from the B-aryl group; however, in this case, the transition
occurs from HOMO to LUMO+1. A second lower intensity, but significant, transition for 12 is
from the HOMO to LUMO, which exhibits a nearly complete charge transfer onto the B-aryl
ring (Figure 6). Thus, compound 12 exhibits a significantly larger Stokes shift than the other
compounds. This phenomenon is further supported by the positive solvatochromism observed for
compound 12, as excited states with strong charge-transfer character are greatly stabilized by
polar solvents. Finally, the nearly complete transfer of electron density to the B-aryl ring in the
LUMO likely yields a more highly twisted TICT structure than the other compounds, which is
reflected in the dramatically decreased quantum yield of emission.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Conclusion
We have synthesized a family of substituted boratriazaroles and have studied their
photophysical and structural properties. Three BN to CC isosteres were prepared, along with one
NH-B to N=C substituted analogue. The boratriazaroles are aromatic, but to a lesser extent
compared to imidazole, triazole, and pyrazole scaffolds. The quantum yield of the model
triphenyl-boratriazarole is significantly lower than the carbon-based analogues, but is shown to
significantly improve upon substitution of one phenyl group with a 2-pyridyl group. This
observation showcases the potential to tune photophysical properties of boratriazaroles. We
subsequently analyzed the electronic and steric influence of the B-aryl ring on the photophysical
properties. While there was not a strong trend between the electronic properties of the B-aryl ring
20
ACS Paragon Plus Environment

Page 21 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
and the quantum yield, the overall aromaticity of the central boratriazarole ring is increased with
electron withdrawing groups. For the most part, the absorption and emission spectra (as well as
the HOMO and LUMO levels) are not greatly influenced by the electronic properties of the B-
aryl ring. The p-CN derivative is the exception to this trend, which has a large bathochromic shift
relative to the other compounds and displays positive solvatochromic behavior. These data
reveals that the boron atom in underexplored boratriazaroles is participating in electronic
communication in the excited state. Judicious choice of the B-aryl substituents (such as the p-CN
derivative disclosed here) can be used to tune the photophysical properties, adding further
understanding to the influence and behaviour of boron containing heterocycles in polyaromatic
systems. In conjunction with these findings, the use of computational tools to assess the
photophysical properties of various substituted boratriazaroles is expected to aid in the
development of new and improved materials.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Experimental Section
2,3,5-triphenyl-2,3-dihydro-1H-1,2,4,3-triazaborole (1). Benzaldehyde (2.0 mL, 19.6 mmol)
was dissolved in 95% ethanol (20 mL) and heated to 75 °C. Phenylhydrazine (10.3 mL, 104.8
mmol) was added dropwise and the reaction is stirred for 1 hour. The reaction was allowed to
cool to room temperature with sustained stirring as the product crystallized out of solution. The
flask was placed in a freezer for 2 hours and the product was filtered, washed with cold ethanol
and dried under high vacuum to yield (E)-1-benzylidene-2-phenylhydrazine (2.01 g, 52%,
white crystals).60 The hydrazonoyl chloride was prepared following literature procedures with
consistent spectral data:44,61 NCS (12.40 g, 92.86 mmol) was dissolved in anhydrous DCM (128
mL) and cooled to 0 °C. Dimethylsulfide (13.8 mL, 188.0 mmol) was added over fifteen
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 33
1
2
3
4
5
6
7
8
9
minutes. After stirring for an additional fifteen minutes, the reaction was cooled to -78 °C and
the hydrazone (6.08 g, 31.00 mmol) dissolved in anhydrous DCM (100 mL) was added dropwise
and allowed to stir at that temperature for 1 hour and warmed to room temperature over 3 hours.
The reaction was quenched with water (20 mL). Ethyl acetate was added and the organic layer
was washed with water, brine, saturated sodium sulfite solution, then water, and dried over
magnesium sulfate. The solution was filtered and slowly concentrated. The product precipitated
or crystallized out of solution during concentration and was filtered to yield pure product. This
process can be repeated to yield multiple crops of product (Z)-N-phenylbenzohydrazonoyl
chloride (4.58 g, 64%, tan solid). The hydrazonoyl chloride (1.50 g, 6.50 mmol) was dissolved
in a minimum amount of methanol and 7N ammonia in methanol (9.3 mL, 65.0 mmol) was
added dropwise and stirred for 4 hours. The volatiles were removed in vacuo and the residue
dissolved in ethyl acetate and washed with water, brine, and dried over sodium sulfate. The red
solution was evaporated and the product purified by column chromatography with a gradient of
100% hexanes to 40% ethyl acetate in hexanes to yield (Z)-N'-phenylbenzohydrazonamide as a
red oil that crystallized over time; the product turned black and may decompose over time (0.766
g, 56%) Mp: 65-70 °C. 1H NMR (500 MHz, CDCl3) δ 7.84 – 7.72 (m, 2H), 7.44 – 7.38 (m, 3H),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
7.30 – 7.22 (m, 2H), 7.12 – 7.04 (m, 2H), 6.92 – 6.83 (m, 1H), 4.83 (br. s, 2H). C NMR (126
MHz, CDCl3) δ 151.3, 147.8, 134.1, 129.9, 129.2, 128.7, 127.5, 125.9, 120.3, 114.5. IR (neat) ν
̃
(cm−1): 3457, 3357, 2928, 1606, 1489, 1384, 824, 750. The hydrazonamide (0.20 g, 0.95 mmol)
and phenyl boronic acid (0.12 g, 0.95 mmol) were dissolved in toluene (3.2 mL). The vessel was
sealed and heated with vigorous stirring to 100 °C for 5 hours. The solution was loaded onto a
plug of silica gel packed with toluene and the product was eluted with toluene. The solvent was
removed in vacuo, and dried thoroughly under high vacuum. The residue was dissolved in a
22
ACS Paragon Plus Environment

Page 23 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
minimum amount of diethylether and layered with hexanes to yield pale yellow feather-like
crystals of 1 (0.144 mg, 50%). Mp: 136 – 138 °C (Et2O/Hexanes). 1H NMR (500 MHz, CDCl3) δ
7.92 – 7.84 (m, 2H), 7.63 – 7.59 (m, 2H), 7.56 – 7.52 (m, 2H), 7.51 (br. s, 1H), 7.49 – 7.45 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
2H), 7.44 – 7.40 (m, 2H), 7.40 – 7.37 (m, 2H), 7.35 – 7.30 (m, 2H), 7.19 – 7.13 (m, 1H). C
NMR (126 MHz, CDCl3) δ 149.0, 143.7, 133.6, 129.9, 129.5, 129.4, 129.0, 128.9, 128.3, 125.5,
11
124.8, 122.1. B NMR (192 MHz, CDCl3) δ 28.0. IR (neat) ν
̃
(cm−1): 3264, 2927, 1600, 1498,
1349, 1069, 824, 783. HRMS (DART) m/z: [M+H]+ calc’d for C19H17BN3 298.1516, found
298.1517.
1,3,5-triphenyl-1H-1,2,4-triazole (2). Product 2 was synthesized according to a modified
literature procedure44 and was consistent with reported spectral data:62 The hydrazonoyl chloride
(0.50 g, 2.17 mmol) was dissolved in DCM (2.2 mL) followed by the addition of benzylamine
(0.71 mL, 6.5 mmol) and triethylamine (0.45 mL, 3.25 mmol) and stirred for 12 hours. The
DCM solution was washed with water, then brine, and dried over magnesium sulfate. The
product was eluted through a plug of silica using a gradient from 100% hexanes to 50% ethyl
acetate in hexanes to yield (Z)-N-benzyl-N'-phenylbenzohydrazonamide as an orange oil
(0.473 g, 72%) that was used immediately in the next step. The hydrazonamide (0.30 g, 1.00
mmol) was dissolved in DCM (10 mL) and Dess-Martin periodinane (0.64 g, 1.50 mmol) was
added portionwise. The solution was stirred for 5 hours, then washed with saturated sodium
bicarbonate solution, brine, and dried over magnesium sulfate. The orange/red crude was
purified by column chromatography with a gradient from hexanes to 25% ethyl acetate in
hexanes to yield 2 as an off-white solid (0.183 g, 62%).
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 33
1
2
3
4
5
6
7
8
9
1,3,5-triphenyl-1H-pyrazole (3). Synthesized according to a modified literature procedure45 and
consistent with reported spectral data.63 Phenylhydrazine (0.71 mL, 7.20 mmol) and iodine (1.83
g, 7.24 mmol) were dissolved in ethanol (120 mL) and chalcone (0.50 g, 2.40 mmol) was added.
The reaction was heated to 100 ºC overnight. The ethanol was evaporated and product
redissolved in ethyl acetate, washed with saturated sodium sulfite solution, brine, then dried over
sodium sulfate. The product was first purified by column chromatography with a gradient from
100% hexanes to 10% ethyl acetate in hexanes and then recrystallized with diethylether/hexanes
to yield 3 as a light yellow solid (0.448 g, 63%).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1,2,4-triphenyl-1H-imidazole (4). Prepared using literature procedure and consistent with
reported spectral data.46 Scale: 2.5 mmol. Pale yellow solid (0.225 g, 30%).
2,4,5-triphenyl-1H-imidazole (5). Prepared using literature procedure47 and consistent with
reported spectral data.64 Scale: 5.0 mmol. White solid (0.444 g, 30%).
Synthesis of hydrazonamides (Z)-N'-phenylpicolinohydrazonamide (6a) and (Z)-N-(4-
bromophenyl)-N'-phenylpicolinohydrazonamide (6b): 2-pyridine carboxaldehyde (10 mL,
105.0 mmol) was dissolved in 95% ethanol (100 mL) and heated to 75 °C. Phenylhydrazine
(10.3 mL, 105.0 mmol) was added dropwise and the reaction was stirred for 1 hour. The reaction
was allowed to cool to room temperature with sustained stirring and the product crystallized out
of solution. The flask was placed in a freezer for 2 hours and the product was filtered, washed
with
cold
ethanol
and
dried
under
high
vacuum
to
yield
(E)-2-((2-
phenylhydrazono)methyl)pyridine (13.6 g, 66%, white crystals).65 The hydrazone (5.0 g, 25.3
24
ACS Paragon Plus Environment

Page 25 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
mmol) was dissolved in a minimum amount of DMF, and NCS (3.58 g, 26.8 mmol) was added
portion-wise over 20 minutes and stirred for 1 hour. Water (two volume equivalents) was added
dropwise and the product precipitated out of solution. The solution was filtered and the filter
cake washed thoroughly with water and dried under high vacuum to yield (Z)-N-
phenylpicolinohydrazonoyl chloride (4.79 g, 82%, amorphous red solid). Mp: 125 – 127 °C.
1H NMR (500 MHz, CDCl3) δ 8.67 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.28 (s, 1H), 8.08 (dt, J = 8.1,
1.1 Hz, 1H), 7.73 (ddd, J = 8.1, 7.4, 1.7 Hz, 1H), 7.37 – 7.30 (m, 2H), 7.27 (ddd, J = 7.4, 4.9, 1.1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
Hz, 1H), 7.24 – 7.19 (m, 2H), 6.98 (tt, J = 7.4, 1.1 Hz, 1H). C NMR (126 MHz, CDCl3) δ
151.5, 149.3, 143.0, 136.4, 129.6, 125.3, 123.6, 121.9, 121.3, 113.8. IR (neat) ν̃
(cm−1): 3147,
2936, 1600, 1493, 1236, 1135, 845, 783. HRMS (DART) m/z: [M+H]+ Calc’d for C12H11ClN3
232.0642, found 232.0642.
Synthesis of 6a: The hydrazonoyl chloride (2.00 g, 8.63 mmol) was dissolved in methanol (10
mL) and 7N ammonia in methanol (9.9 mL, 69.1 mmol) was added dropwise and stirred for 4
hours. The solvent was evaporated and the residue dissolved in ethyl acetate. The organic layer
was washed two times with water, followed by a brine wash, then dried over sodium sulfate. The
volatiles were removed in vacuo and the resultant red oil was dried under high vacuum and
crystallized over multiple days (1.79 g, 98%, red crystals). Mp: 51 – 55 °C. 1H NMR (500 MHz,
CDCl3) δ 8.53 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H), 8.27 (dt, J = 8.1, 1.1 Hz, 1H), 7.72 (ddd, J = 8.1,
7.4, 1.7 Hz, 1H), 7.33 – 7.26 (m, 3H), 7.20 – 7.13 (m, 2H), 6.89 (t, J = 7.3 Hz, 1H), 6.43 (s, 1H),
5.36 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 150.7, 148.1, 147.1, 146.1, 136.5, 129.3, 129.1,
124.0, 121.0, 120.4, 114.2. IR (neat) ν̃
(cm−1): 3423, 3330, 3051, 1587, 1495, 1247, 881, 788.
HRMS (DART) m/z: [M+H]+ Calc’d for C12H13N4 213.1140, found 213.1139.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 33
1
2
3
4
5
6
7
8
9
Synthesis of 6b: The hydrazonoyl chloride (0.20 g, 0.86 mmol) and p-bromoaniline (0.22 g, 1.29
mmol) were dissolved in THF (2.9 mL) and triethylamine (0.30 mL, 2.16 mmol) was added. The
solution was stirred for two days until complete by TLC. The volatiles were evaporated and the
residue dissolved in ethyl acetate and washed with water, brine, then dried over sodium sulfate.
The product was purified by column chromatography with a gradient from hexanes to 25% ethyl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
acetate in hexanes to yield an orange-yellow solid (0.274 g, 87%). Mp: 140 – 143 °C. H NMR
(500 MHz, CDCl3) δ 8.48 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H), 8.30 (dt, J = 8.1, 1.1 Hz, 1H), 7.77 –
7.70 (m, 2H), 7.39 – 7.35 (m, 2H), 7.29 – 7.25 (m, 2H), 7.23 (ddd, J = 7.4, 4.9, 1.2 Hz, 1H), 7.12
13
– 7.08 (m, 2H), 7.06 (br. s, 1H), 6.88 (tt, J = 7.4, 1.1 Hz, 1H), 6.72 – 6.67 (m, 2H). C NMR
(126 MHz, CDCl3) δ 152.1, 148.1, 144.5, 139.2, 136.6, 135.2, 132.1, 129.4, 123.2, 120.6, 120.1,
120.0, 114.1, 113.2. IR (neat) ν̃
(cm−1): 3335, 2929, 1599, 1489, 1069, 878, 783. HRMS (DART)
m/z: [M+H]+ Calc’d for C18H16BrN4 367.0558, found 367.0559.
General procedure for the synthesis of boratriazaroles: Hydrazonamide (1 equiv) and boronic
acid (1 equiv) were dissolved in toluene (0.3 M). The reaction mixture was heated to 100 °C and
stirred for 6 – 12 hours until completion, as indicated by TLC analysis. Upon completion, the
reaction mixture was cooled to room temperature, loaded directly onto a silica gel plug and
eluted with toluene. The toluene was removed in vacuo and the product subsequently
recrystallized in diethylether layered with hexanes to afford pure product.
2-(3-(4-methoxyphenyl)-2-phenyl-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine
(7).
Scale: 0.9 mmol. Recrystallized in Et2O to yield clear, colorless crystals (126 mg, 42%). Mp: 110
– 112 °C. 1H NMR (400 MHz, CDCl3) δ 8.60 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H), 8.52 (s, 1H), 8.21
26
ACS Paragon Plus Environment

Page 27 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
(dt, J = 8.0, 1.1 Hz, 1H), 7.81 – 7.72 (m, 1H), 7.62 – 7.49 (m, 4H), 7.39 – 7.32 (m, 2H), 7.29
(ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 7.19 (ddt, J = 8.6, 6.9, 1.2 Hz, 1H), 6.95 – 6.87 (m, 2H), 3.84 (s,
7
8
13
3H). C NMR (126 MHz, CDCl3) δ 160.8, 149.3, 149.0, 148.1, 143.9, 136.8, 135.3, 129.0,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
125.1, 123.7, 122.7, 120.4, 113.9, 55.2. 11B NMR (128 MHz, CDCl3) δ 27.7. IR (neat) ν (cm−1):
̃
3460, 3056, 2932, 1599, 1498, 1453, 1412, 1346, 1396, 1243. HRMS (DART) m/z: [M+H]+
Calc’d for C19H17BN4O 329.1574, found 329.1569.
2-(2-phenyl-3-(p-tolyl)-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine (8). Scale: 0.9
mmol. Recrystallized in Et2O/Hexanes to yield clear, colorless crystals (58 mg, 20%). Mp: 105 –
108 °C. 1H NMR (400 MHz, CDCl3) δ 8.60 (dt, J = 5.1, 1.4 Hz, 1H), 8.54 (s, 1H), 8.22 (dt, J =
8.0, 1.1 Hz, 1H), 7.77 (td, J = 7.8, 1.7 Hz, 1H), 7.58 – 7.49 (m, 4H), 7.37 – 7.32 (m, 2H), 7.29
(ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 7.21 – 7.15 (m, 3H), 2.38 (s, 3H). 13C NMR (126 MHz, CDCl3) δ
149.3, 149.0, 148.1, 143.8, 139.5, 136.8, 133.8, 129.0, 129.0, 125.1, 123.8, 122.6, 120.4, 21.7.
11B NMR (128 MHz, CDCl3) δ 27.8. IR (neat) ν (cm−1): 3465, 3054, 2923, 1592, 1479, 1459,
̃
1410, 1346, 806, 766. HRMS (DART) m/z: [M+H]+ Calc’d for C19H17BN4 313.1625, found
313.1617.
2-(2,3-diphenyl-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine (9). Scale: 0.9 mmol.
Recrystallized in Et2O/Hexanes to yield clear, orange crystals (135 mg, 51%). Mp: 76 – 78 °C.
1H NMR (400 MHz, CDCl3) δ 8.60 (ddd, J = 4.9, 1.8, 1.0 Hz, 1H), 8.58 (br. s, 1H), 8.23 (dt, J =
8.0, 1.1 Hz, 1H), 7.77 (td, J = 7.7, 1.7 Hz, 1H), 7.65 – 7.59 (m, 2H), 7.58 – 7.52 (m, 2H), 7.44 –
7.32 (m, 5H), 7.30 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 7.22 – 7.15 (m, 1H). 13C NMR (126 MHz,
CDCl3) δ 149.3, 149.1, 148.1, 143.7, 136.8, 133.7, 129.5, 129.0, 128.2, 125.1, 123.8, 122.6,
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 33
1
2
3
4
5
6
11
120.4. B NMR (128 MHz, CDCl3) δ 28.0. IR (neat) ν
1340, 752, 702. HRMS (DART) m/z: [M+H]+ Calc’d for C18H15BN4 299.1468, found 299.1471.
̃
(cm−1): 3231, 2959, 1596, 1494, 1418,
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(3-(4-chlorophenyl)-2-phenyl-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine
(10).
Scale: 0.47 mmol. Recrystallized in Et2O to yield clear, orange crystals (59.9 mg, 38%). Mp: 111
– 114 °C. 1H NMR (500 MHz, CDCl3) δ 8.60 (ddd, J = 4.9, 1.7, 1.0 Hz, 1H), 8.59 (s, 1H), 8.21
(dt, J = 8.0, 1.1 Hz, 1H), 7.77 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 7.57 – 7.52 (m, 2H), 7.52 – 7.48
(m, 2H), 7.41 – 7.32 (m, 4H), 7.30 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 7.24 – 7.16 (m, 1H). 13C NMR
(126 MHz, CDCl3) δ 149.4, 149.1, 147.9, 143.5, 136.9, 135.8, 135.1, 129.1, 128.5, 125.4, 123.9,
11
122.6, 120.4. B NMR (160 MHz, CDCl3) δ 27.2. IR (neat) ν
̃
(cm−1): 3456, 3057, 1590, 1474,
1343, 1284, 1083, 813, 781. HRMS (DART) m/z: [M+H]+ Calc’d for C18H15BClN4 333.1078,
found 333.1082.
2-(3-(4-fluorophenyl)-2-phenyl-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine (11). Scale:
0.9 mmol. Recrystallized in 1:1 DCM/Hexanes to yield clear, orange crystals (147 mg, 50%).
Mp: 112 – 115 °C. 1H NMR (400 MHz, CDCl3) δ 8.60 (ddd, J = 4.9, 1.8, 1.0 Hz, 1H), 8.56 (br.
s, 1H), 8.21 (dt, J = 8.0, 1.1 Hz, 1H), 7.77 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 7.63 – 7.55 (m, 2H),
7.54 – 7.47 (m, 2H), 7.38 – 7.32 (m, 2H), 7.30 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 7.20 (ddt, J = 7.9,
6.9, 1.2 Hz, 1H), 7.12 – 7.00 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 163.9 (d, J = 248.9 Hz),
149.3, 149.1, 148.0, 143.6, 136.9, 135.7 (d, J = 7.7 Hz), 129.1, 125.3, 123.9, 122.7, 120.4, 115.4
(d, J = 20.1 Hz). 11B NMR (128 MHz, CDCl3) δ 27.7. 19F NMR (377 MHz, CDCl3) δ -110.9. IR
(neat) ν̃
(cm−1): 3451, 3054, 1596, 1496, 1413, 1342, 1214, 837, 767. HRMS (DART) m/z:
[M+H]+ Calc’d for C18H14BFN4 317.1374, found 317.1376.
28
ACS Paragon Plus Environment

Page 29 of 33
The Journal of Organic Chemistry
1
2
3
4
5
6
4-(2-phenyl-5-(pyridin-2-yl)-2,4-dihydro-3H-1,2,4,3-triazaborol-3-yl)benzonitrile
(12).
7
8
9
Scale: 0.47 mmol. Recrystallized in Et2O to yield clear, pale orange crystals (96.3 mg, 63%).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Mp: 126 – 128 °C. H NMR (500 MHz, CDCl3) δ 8.70 (br. s, 1H), 8.60 (ddd, J = 4.9, 1.7, 1.0
Hz, 1H), 8.22 (dt, J = 8.0, 1.1 Hz, 1H), 7.79 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 7.73 – 7.68 (m, 2H),
7.67 – 7.61 (m, 2H), 7.50 – 7.43 (m, 2H), 7.40 – 7.34 (m, 2H), 7.32 (ddd, J = 7.5, 4.9, 1.2 Hz,
1H), 7.25 – 7.21 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 149.6, 149.1, 147.7, 143.1, 137.0,
11
134.2, 131.6, 129.2, 125.7, 124.1, 122.7, 120.4, 119.0, 113.1. B NMR (160 MHz, CDCl3) δ
26.9. IR (neat) ν̃
(cm−1): 3272, 2927, 2166, 1600, 1494, 1341, 1091, 832, 765. HRMS (DART)
m/z: [M+H]+ Calc’d for C19H15BN5 324.1421, found 324.1430.
2-(3-(2,6-difluorophenyl)-2-phenyl-3,4-dihydro-2H-1,2,4,3-triazaborol-5-yl)pyridine (13).
Scale: 0.471 mmol. Recrystallized in Et2O/Hexanes to yield clear, off-white crystals (50 mg,
32%). Mp: 110 – 113 °C. 1H NMR (500 MHz, CDCl3) δ 8.76 (s, 1H), 8.60 (ddd, J = 4.9, 1.8, 1.0
Hz, 1H), 8.24 (dt, J = 8.0, 1.1 Hz, 1H), 7.78 (ddd, J = 8.0, 7.5, 1.7 Hz, 1H), 7.52 – 7.45 (m, 2H),
7.41 (tt, J = 8.3, 6.7 Hz, 1H), 7.35 – 7.28 (m, 3H), 7.21 – 7.13 (m, 1H), 6.99 – 6.85 (m, 2H). 13C
NMR (126 MHz, CDCl3) δ 165.3 (dd, J = 247.3, 12.6 Hz), 149.8, 149.1, 147.8, 143.8, 136.9,
132.5 (t, J = 10.3 Hz), 128.9, 125.0, 123.9, 121.1, 120.4, 112.4 – 110.7 (m). 11B NMR (160 MHz,
CDCl3) δ 24.5. 19F NMR (376 MHz, CDCl3) δ -99.9. IR (neat) ν (cm−1): 3234, 2928, 1596, 1500,
̃
1343, 1227, 1118, 1105, 982, 785. HRMS (DART) m/z: [M+H]+ Calc’d for C18H14BF2N4
335.1280, found 335.1286.
29
ACS Paragon Plus Environment