Synthesis of Bicyclic Boron Heterocycles Containing [1,3,4,2]Oxadiazaborole and [1,3,2]Oxazaborine

Article abstract of DOI:10.1055/s-0035-1562610

Boron triacetate, generated in situ, reacts with various 3-(2-acylhydrazono)-2-(2-phenylhydrazono)butanoic acids to give 4-acetoxy-2-aryl-8-methyl-6-oxo-7-phenylhydrazono-2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborines in good yields. These derivatives represent a class of new zwitterionic, tetrahedral boron heterocycles. X-ray single-crystal analyses of one of the starting (acylhydrazono)butanoic acids as well as of one heterocyclic boron product are reported.

Full text of DOI:10.1055/s-0035-1562610

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–I
paper
A
A. Kotali et al.
Paper
Synthesis
Synthesis of Bicyclic Boron Heterocycles Containing [1,3,4,2]Oxa-
diazaborole and [1,3,2]Oxazaborine
Antigoni Kotali*a
Anna Maniadakia
Elvira Kotalia
Philip A. Harrisb
Ewa Różycka-Sokołowskac
Piotr Bałczewskic,d
John A. Joulee
Me
Me
Me
RCONHNH2
Ph
MeOH
H
+
N
O
N
O
Ph
R
N
N
O
Ph
H3BO3, Ac2O
reflux, 2 h
N
O
O
N
N
N
N
N
reflux, 2 h
H
H
H
R
-
B
O
HO
77–98%
55–57%
O
HO
Me
O
9 examples
O
a Laboratory of Organic Chemistry, Department of Chemical
Engineering, University of Thessaloniki, Thessaloniki
54124, Greece
kotali@eng.auth.gr
b GlaxoSmithKline, 1250 South Collegeville Road, P.O. Box
5089, Collegeville, PA 19426-0989, USA
c Institute of Chemistry, Environmental Protection and
Biotechnology, Jan Długosz University in Częstochowa,
42-201 Częstochowa, Poland
d Department of Heteroorganic Chemistry, Centre of
Molecular and Macromolecular Studies, Polish Academy
of Sciences, 90-363 Łódz, Poland
e The School of Chemistry, The University of Manchester,
Manchester M13 9PL, UK
Received: 24.06.2016
Accepted after revision: 11.07.2016
Published online: 17.08.2016
periodic table adjacent to carbon make trivalent boron
compounds behave as electrophilic molecules with trigonal
planar structures that are neutral, yet isoelectronic to car-
bocations. However, formation of an additional bond to bo-
ron generates anionic tetravalent boron compounds that
have tetrahedral structures and behave as nucleophilic mol-
ecules. Most notably, both of these types of boron com-
pounds can be stable while retaining significant reactivity
that defines their unique, versatile, interconvertible, and
tunable chemical behavior.3–6 A variety of stable boron het-
erocycles have been designed and synthesized, most of
them stabilized by some degree of heteroaromaticity. Much
progress has been made in the last decade in boron hetero-
cycles.4,7 Several excellent reviews have appeared in the lit-
erature, highlighting developments in the chemistry of bo-
ron heterocycles.1–6
Moreover, small molecules containing boron have been
found to have significant biological properties, including
anticancer and antibacterial activities.3,5,7 The FDA has ap-
proved the first two boron-containing drugs ever brought
to market: Velcade (bortezomib) for treating multiple my-
eloma8 and Kerydin (tavaborole) as a topical antifungal
solution for treating onychomycosis (Figure 1).9
DOI: 10.1055/s-0035-1562610; Art ID: ss-2016-n0259-op
Abstract Boron triacetate, generated in situ, reacts with various 3-(2-acyl-
hydrazono)-2-(2-phenylhydrazono)butanoic acids to give 4-acetoxy-2-
aryl-8-methyl-6-oxo-7-phenylhydrazono-2H,4H,6H,7H,8H-[1,3,4,2]oxa-
diazaborolo[2,3-b][1,3,2]oxazaborines in good yields. These derivatives
represent a class of new zwitterionic, tetrahedral boron heterocycles. X-
ray single-crystal analyses of one of the starting (acylhydrazono)buta-
noic acids as well as of one heterocyclic boron product are reported.
Key words hydrazones, cyclocondensation, boron heterocycles, bo-
ron triacetate, [1,3,4,2]oxadiazaboroles, [1,3,2]oxazaborines
Organic compounds containing boron have been known
for over a century and the usefulness of boron in heterocy-
clic chemistry is enormous. A growing number of boron-
mediated reactions have become vital tools for synthetic
chemistry, particularly in asymmetric synthesis, metal-cat-
alyzed processes, acid catalysis, and multicomponent reac-
tions.1,2 The well-known Suzuki cross-coupling reaction has
attracted a lot of attention and has been widely applied as a
general method for palladium-catalyzed C–C bond forma-
tion. In this valuable synthetic reaction, the boron atom of a
boronic acid or ester is not incorporated into the product.1–3
On the other hand, the presence of boron in a molecule
could be valuable due to its unique properties. The elec-
tronic structure of boron and its strategic position in the
Hydrazone derivatives have also been reported to ex-
hibit a wide variety of biological activities,10,11 among them
appreciable anticancer12–15 as well as antifungal15,16 activi-
ties.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

B
A. Kotali et al.
Paper
Synthesis
H
O
H
O
1. NaNO2, HCl, H2O
2. MeCO2Na, H2O,
MeCOCH2CO2Et, EtOH
Me
Me
B
NNHPh
CO2Et
O
PhNH2
H
N
75%
OH
O
Me
N
H
N
B
1
NaOH
CH2Cl2
MeOH
2
O
N
O
F
AlCl3 65%
Velcade
Kerydin
Me
N
Me
Ph
NNHPh
CO2Na
Figure 1 Boron-containing drugs
O
N
O
HCl, H2O
H
70%
(from 2)
HO
O
3
4
The combination of hydrazones with other functional
groups leads to compounds with unique physical and
chemical character.11,12,17 Owing to their biological and
pharmacological properties, they are considered important
for the synthesis of heterocyclic compounds.11,12
Me
RCONHNH2
MeOH
reflux, 2 h
H
N
N
R
N
O
Ph
N
H
O
77–98%
HO
Furthermore, β-keto acids are well known molecules in-
volved in biological processes. For example, acetoacetate
and 2-methylacetoacetate are accumulated in metabolic
disorders such as diabetes and isoleucinemia.18 β-Keto acids
are also very useful as synthons, since they can act as stabi-
lized ketone enolates and react with suitable electrophilic
substrates.19 Thus they have been proved valuable building
blocks for the synthesis of several classes of compounds
with different biological activities.20 In addition, the study
of amine-catalyzed decarboxylations of β-keto acids occu-
pies a special place in the history of bioorganic chemistry
and enzymology.21 Recently, efficient construction of tertia-
ry and quaternary centers has been achieved via rhodium-
catalyzed chemo- and regioselective decarboxylative addi-
tion of β-keto acids to allenes.22
5
Me
H3BO3, Ac2O
reflux, 2 h
+
N
Ph
N
O
N
B
O
N
H
R
-
55–87%
O
O
Me
O
6
Scheme 1 Synthesis of boron heterocycles 6
and sodium hydroxide for a few minutes at room tempera-
ture. The methodology worked smoothly in our case, and
acid 4 was isolated in 70% overall yield from ester 2.
Subsequently, 3-(2-acylhydrazono)-2-(2-phenylhydra-
zono)butanoic acids 5 were synthesized via treatment of β-
keto acid 4 with the appropriate hydrazide, in a molar ratio
of 1:1, in propanol under reflux for two hours, as depicted
in Scheme 1 and Table 1.
On the basis of the above information and our interest23
in boron heterocycles as well as hydrazone substrates,24 we
designed the synthesis of compounds of type 6, which con-
tain both boron and hydrazone moieties, starting from 2-
hydrazono β-keto acid 4 (Scheme 1).
Table 1 New Synthesized Compounds 5 and 6
The starting substrate, 3-oxo-2-(2-phenylhydrazo-
no)butanoic acid25 (4) was prepared in two steps via initial
diazotization of aniline (1) and reaction of the obtained di-
azonium salt with ethyl acetoacetate to give ethyl 3-oxo-2-
(2-phenylhydrazono)butanoate (2) (Scheme 1).26 Subse-
quently, processing of ethyl ester 2 led to the formation of
the desired substrate 4 via two alternative methods. Specif-
ically, the first method involved successful conversion of
ethyl ester 2 into 4 in 65% yield, by treatment with anhy-
drous aluminum trichloride in either chlorobenzene or eth-
ylbenzene. This result is in direct contradiction of the re-
port that cinnolines are obtained by an analogous proce-
dure.27 The second method proceeded via the application of
the methodology of Theodorou et al. for the alkaline hydro-
lysis of esters.28 This is a very mild and rapid procedure for
the efficient alkaline hydrolysis of esters under non-aque-
ous conditions, by using dichloromethane/methanol (9:1)
Entry
Compound
R
Yield (%) of 5 Yield (%) of 6
1
2
3
4
5
6
7
8
9
5a, 6a
5b, 6b
5c, 6c
5d, 6d
5e, 6e
5f, 6f
Ph
96
92
97
96
95
98
97
92
77
56
59
55
63
83
87
58
55
61
4-MeC6H4
4-ClC6H4
4-NO2C6H4
2-NO2C6H4
2-furyl
2-thienyl
Bn
5g, 6g
5h, 6h
5i, 6i
Me
The hydrazones 5a–h were obtained in excellent yields
(92–98%), and 5i (R = Me) in a good yield (77%) (Table 1).
Hydrazones 5 were subsequently treated with boron triace-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

C
A. Kotali et al.
Paper
Synthesis
tate (strictly speaking, acetic acid anhydride with boric
acid) generated in situ, via the reaction of boric acid with
acetic anhydride. The reactions were performed under re-
flux to form the desired products 6 in good yields (55–87%).
Boron heterocycles 6 were purified by column chroma-
tography and further recrystallization from either chloro-
form/petroleum ether or dichloromethane/petroleum
ether. Hydrazones 5a–i as well as products 6a–i are new
compounds and their structures were established by their
IR, 1H and 13C NMR, and mass spectra, as well as by their el-
emental analyses. Additionally, X-ray crystal structure anal-
yses were carried out for 5f and 6f.
two-proton singlet at 2.46 and 2.34 ppm respectively, and
an additional one-proton singlet at 11.44 and 11.86 ppm,
respectively. Hydrazones 5f (R = 2-furyl) and 5g (R = 2-thie-
nyl) gave a one-proton singlet and one two-proton singlet
in the range 2.36–2.45 ppm, whereas 5f gave a three-pro-
ton singlet at 2.44 ppm when subjected to variable-tem-
perature 1H NMR at 105 °C.
Table 2 Geometrical Parameters for Non-covalent Interactions in 5f
and 6f·CHCl3
X–Y···Aa,b
X–Y [Å]
Y···A [Å]
X···A [Å]
X–Y···A [°]
In the IR spectra of 5, characteristic absorptions ap-
peared at 3427–3443 (for NH and OH stretching), 3149–
3094 (for =CH and C–H bonds), and 1721–1728 cm–1 (for
C=O and C=N bond stretching).
5f
N4–H4A···O25
O9–H9A···N5
N12–H12A···O10
C19–H19A···N11
0.91(2)
0.95(3)
0.94(2)
0.97(2)
2.32(2)
1.61(3)
1.86(2)
2.42(2)
2.699(2)
2.501(2)
2.605(2)
2.772(2)
104(1)
154(2)
134(2)
101(2)
N4–H4A···O9(i)
0.91(2)
0.92(2)
0.93
2.38(2)
2.56(2)
2.57
3.288(2)
3.388(3)
3.403(2)
176(2)
150(2)
150
C19–H19C···O10(i)
C18–H18···O10(ii)
C3–O2···Cg1(iii)
6f
1.218(2)
3.787(1)
3.786(2)
80.67(9)
N12–H12A···O10
C19–H19A···N4
C29–H29···O25
C29–H29···N4
N12–H12A···O10(i)
C18–H18···O9(i)
C19–H19C···Cg1(i)
0.92(3)
0.92(4)
0.95(4)
0.95(4)
0.92(3)
0.93
2.03(3)
2.56(3)
2.57(4)
2.59(4)
2.51(3)
2.54
2.661(2)
2.929(3)
3.222(3)
3.501(4)
3.367(2)
3.422(2)
3.639(2)
125(3)
105(3)
126(3)
163(4)
155(3)
160
0.88(4)
2.87(4)
147(3)
a Cg1 are centroids of benzene rings.
b Symmetry codes: 5f: (i) x, 1 – y, –1/2 + z; (ii) –x, y, 3/2 – z; (iii) –x, 1 – y, 1 –
z; 6f: (i) –1 – x, –y, 1 – z.
In their 13C NMR spectra, most of compounds 5, except
5c and 5d, appear to be a mixture of two isomers. Charac-
teristic signals appeared at 12.3–17.0 ppm, assigned to
methyl carbons attached at the C=N carbon. The signals at
the highest δ values, 143.3–168.5, were assigned to the car-
boxyl carbon CO2H and to the amide carbonyl carbon
NHCO, whereas those at 133.2–156.7 ppm were assigned to
the hydrazono carbon C=N. In the 13C NMR spectrum of 5g
there is not exact duplication for the aromatic carbons and
the spectrum is complicated by broadening of the peaks. It
is suggested that some of the peaks are overlapping. It is
also possible that some of the small quaternary carbons
may be hidden in the baseline noise. Moreover, in the 13C
NMR spectrum of 5h one of the two peaks assigned to the
CH2 group appears at 40.5 ppm, whereas the other is over-
lapping with DMSO peaks. Furthermore, when hydrazone
5f was subjected to variable temperature 13C NMR, coales-
cence of the signals to one diastereoisomer was observed at
105 °C.
Figure 2 (A) View of 5f, showing the atom numbering scheme and in-
tramolecular hydrogen bonds (black dashed lines); displacement ellip-
soids are drawn at the 30% probability level. (B) Part of the crystal
structure of 5f, showing the N–H···O (blue dashed line), C–H···O (red
and green dashed lines), and C=O···π (black dashed line) intermolecular
interactions; all H atoms not involved in these interactions have been
omitted for clarity, and the Cg1 centroids of benzene rings are denoted
by small black spheres. Symmetry codes i–iii are given in Table 2.
1
The H NMR spectra of the new hydrazones 5 were in
some cases rather complicated due to the formation of sev-
eral hydrogen bonds as shown by the X-ray analysis shown
in Figure 2. Thus, the protons of the methyl at C=N for 5a
(R = Ph), 5c (R = 4-ClC6H4), 5h (R = Bn), and 5i (R = Me) gave
a characteristic three-proton singlet in the range 2.08–2.45
ppm, as expected, whereas in the other hydrazones these
methyl proton signals showed two peaks. Specifically, hy-
drazones 5b (R = p-tolyl) and 5e (R = o-nitrophenyl) gave a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

D
A. Kotali et al.
Paper
Synthesis
Finally, hydrazones 5 showed prominent ions corre-
sponding to [M + H]+ in their mass spectra.
dashed lines, respectively, in Figure 3; Table 2). The boron
atom of 6f is present in a distorted tetrahedral coordination
environment with three oxygen atoms and one nitrogen
atom as coordinating atoms (Figure 3 A). As can be seen in
Figure 3 A, there are two intramolecular hydrogen bonds
(black dashed line; Table 2) forming the finite motifs. Apart
from the above-mentioned non-covalent interactions in the
crystal structure of 6f·CHCl3, there is one N12–H12A···O10(i)
hydrogen bond (blue dashed line in Figure 3 B), which con-
nects two molecules 6f into a centrosymmetric dimer,
which is additionally stabilized by the weaker C18–
H18···O9(i) hydrogen bond (green dashed line). Each such di-
mer is connected with two others by the C-H···π hydrogen
bond (black dashed line; Table 2), so forming a tape parallel
to the crystallographic axis b. The molecules of adjacent
tapes are further linked by the slipped π···π interactions
(grey solid line) with distances between centroids of aro-
matic rings lying in the range of 3.584(1)–3.788(1) Å.
An X-ray diffraction analysis was carried out on hydra-
zone 5f. The structure that was found by X-ray crystallogra-
phy is shown in Figure 2 A. The furan ring together with at-
oms numbered 2–8 and 10–12 lie practically in one plane
(the largest out-of-plane deviation is 0.090(1) Å for atom
C6). Atoms C19 and O9 deviate from this plane by 0.326(2)
and –0.186(1) Å, respectively, and the plane formed by the
benzene ring is inclined relative to it at an angle of only
8.76(4)°. There are four intramolecular hydrogen bonds (Ta-
ble 2), which form the finite motifs with descriptors29 given
in Figure 2 A. In the crystal structure the molecules are
linked by the N4–H4A···O9(i) hydrogen bond (blue dashed
line in Figure 2 B) into a simple C(7) chain running parallel
to the crystallographic axis c, and additionally stabilized by
the weaker C19–H19C···O10(i) hydrogen bond (red dashed
lines). The latter interaction can be described by the graph-
set notation C(6). Molecules belonging to the two C(7)
chains are connected by the C18–H18C···O10(ii) hydrogen
bond (green dashed line), which on the first-level graph-set
2
is classified as R2 (16). The combined effect of these three
different hydrogen bonds is a one-dimensional framework
in the form of an infinite tape parallel to the above axis, and
additionally stabilized by the C=O···π interaction (black
dashed line; Table 2).
In the IR spectra of 6, characteristic absorptions ap-
peared at 3418–3449 (for the B–N bond), 3092–3132 (for
the N–H bond), 1723–1654 (for the acetoxy C=O bond), and
1692–1460 cm–1 (for lactone C=O and C=N bonds).
1
In the H NMR spectra of the new boron compounds 6
there were two characteristic three-proton singlets in the
ranges 1.91–2.01 and 2.66–2.80 ppm, assigned to the meth-
yl at C5 and to the methyl protons of the acetoxy group, re-
spectively. A characteristic singlet, due to the proton of the
NH group appeared at 13.70–14.31 ppm.
In the 13C NMR spectra of compounds 6, characteristic
resonances appeared at 13.8–14.1 ppm and can be assigned
to the methyl groups attached at the C=N carbon and at
21.8–23.0 ppm, which are assigned to the methyl of the ac-
etoxy group. The signals at the lowest field values at 175.2–
162.6 ppm are assigned to the ester C=O carbon as well as
to the lactone C=O carbon, whereas the signals due the C=N
carbons appeared at values of 165.0–140.9 ppm. Finally, bo-
ron derivatives 6 showed prominent peaks corresponding
to the ion [M – OCOCH3] in their mass spectra.
An X-ray diffraction analysis was carried out on boron
derivative 6f. It was found that this compound crystallizes
as a chloroform solvate (6f·CHCl3), with one molecule 6f
and one molecule of solvent in the asymmetric unit (Figure
3 A). These molecules are connected by the C29–H29···N4
and C29–H29···O10 hydrogen bonds (sky blue and red
Figure 3 (A) View of 6f·CHCl3, showing the tetrahedral environment
around the boron atom and the atom numbering scheme; displace-
ment ellipsoids are drawn at the 30% probability level and the intramo-
lecular hydrogen bonds are denoted by black dashed lines. (B) Part of
the crystal structure of 6f·CHCl3 showing the N–H···O, C–H···O, C–H···N
and C–H···π hydrogen bonds (blue, red and green, sky blue, and black
dashed lines, respectively) and the π···π stacking interactions (grey sol-
id line); all H atoms not involved in the hydrogen bonds have been
omitted for clarity and the Cg1 centroids of benzene rings are denoted
by small black spheres. The minor component of a disorder on Cl atoms
has been omitted. Symmetry codes: (i) is given in Table 2; (ii) –1 – x,
1 – y, 1 – z; (iii) 1 – x, –y, –z; (iv) –x, –y, 1 – z.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

E
A. Kotali et al.
Paper
Synthesis
Concerning the mechanism of the reaction, we suggest
that it proceeds via intermediates 7 and 8, as shown in
Scheme 2, by analogy to the way we have recently suggest-
ed for the formation of substituted oxadiazaborolo[2,3-
b][3,4-e]pyrano[1,3,2]oxazaborines.23
plates were Merck plastic plates with silica gel 60F254 (70–230 mesh).
Melting points were recorded by using a Fischer Scientific melting
point measurement apparatus. IR spectra were recorded on an FTIR
Nicolet 200 spectrometer. 1H (400 MHz) and 13C (100 MHz) NMR
spectra were recorded on a Bruker Avance 400 instrument and the
chemical shifts δ are reported relative to either CDCl3, (δ = 7.30 and
77.0 for 1H and 13C NMR, respectively) or DMSO-d6 (δ = 2.50 and 39.5
for 1H and 13C NMR, respectively). 11B (160 MHz) NMR spectra were
recorded on a Bruker AV III 500 and the chemical shifts δ are reported
relative to B(OH)3–D2O (δ = 19.5). Mass spectra were obtained on a
Platform II spectrometer.
Me
Me
H
H
R
N
N
O
Ph
R
N
N
O
Ph
B(OAc)3
– AcOH
N
N
N
N
H
H
O
O
B
O
HO
OAc
AcO
Diffraction data for 5f and 6f were collected using an Oxford Diffrac-
tion XcaliburTM 3 diffractometer. The structures were solved by direct
methods and refined by full-matrix least-squares on F2 with SHELX-
97.33 The non-hydrogen atoms were refined anisotropically. All aro-
matic hydrogen atoms were positioned geometrically and con-
strained to ride on their parent atoms, with Uiso(H) values of 1.2
5
7
H
Me
R
N
N
O
Ph
+
6
N
B
N
H
– AcOH
– AcOH
O
O
O
Ac
U
eq(Caromatic). H atoms bonded to C23 in 5f were included in the refine-
8
ment at geometrically idealized positions, with C–H distances of 0.96
and with Uiso(H) = 1.5Ueq(Cmethyl). Other H atoms located in difference
maps and refined isotropically.
Scheme 2 Proposed mechanism of the synthesis of boron heterocy-
cles 6
3-Oxo-2-(2-phenylhydrazono)butanoic Acid (4)
It is relevant to compare the structures of our new bo-
ron heterocycles to some simpler structures previously re-
ported. Thus, the imines formed from salicylaldehyde and
amino acids react with phenylboronic acid to gives struc-
tures 9 (Figure 4).30 Structures such as 10 are similarly de-
rived from imines of o-hydroxyanilines (Figure 4).31 Phenyl-
boronic acid reacts with N-alkyl-N-(2-hydroxyethyl)-2-
aminoacetic acids to generate the bicycles 11 (Figure 4).32 It
is significant for our future biological investigations of our
new boron heterocycles that compounds 9 were shown to
be inhibitors of the enzyme human neutrophile elastase.30
Method A: A mixture of ethyl ester 2 (2.34 g, 10 mmol) and AlCl3 (2.67
g, 20 mmol) in either chlorobenzene or ethylbenzene (30 mL) was re-
fluxed for 1 h. The reaction mixture was allowed to cool and subse-
quently it was poured into 37 % w/w aq HCl (50 mL). The solid prod-
uct was collected by filtration, washed with H2O to neutral pH, and
dried in desiccator and under vacuum. Recrystallization from xylene
afforded 4 as yellow crystals.
Yield: 1.34 g (65%); mp 157–158 °C (from xylene); mp 149–150 °C
(from AcOH) [Lit.25 149 °C (from AcOH)].
Method B: A mixture of ethyl ester 2 (500 mg, 2.14 mmol) and NaOH
(128 mg, 3.21 mmol) in a mixture of CH2Cl2 (14.4 mL) and MeOH (1.6
mL) (9:1) was stirred for 3 h. The solid product 3 was collected by fil-
tration and subsequently dissolved in aq HCl (1 N, 100 mL); it was
then extracted with CH2Cl2. The organic layer was dried with Na2SO4.
Evaporation of the solvent afforded 4 as yellow crystals.
R
R
+
+
+
N
N
N
O
O
–
–
–
B
B
B
O
O
O
O
O
O
Yield: 308 mg (70%); mp 157–158 °C.
9
10
11
Hydrazones 5; General Procedure
Figure 4 Zwitterionic boron compounds
A mixture of butanoic acid 4 (500 mg, 4.85 mmol) and the appropri-
ate hydrazide RCONHNH2 (1 equiv) was heated at reflux in PrOH (20
mL) for 2 h. The mixture was allowed to cool and the precipitate that
formed was collected by filtration and dried under vacuum in a desic-
cator to afford the corresponding pure N-acylhydrazone 5 as a white
solid.
The starting substituted β-keto acid 4 has been used in a
two-step straightforward preparation of novel zwitterionic
boron derivatives in very good yields via the initial forma-
tion of hydrazone derivatives 5. The novel boron heterocy-
cles could possibly demonstrate interesting biological activ-
ity, since they incorporate several biological features such
as an ionic tetrahedral boron structure as well as multiple
hydrazone C=N bonds in their structures. The presence of
oxo and phenylhydrazono moieties at C6 and C7 and the ex-
tended π-electronic circuit that is created give them the
ability to possibly serve as materials for organic electronics.
3-(2-Benzoylhydrazono)-2-(2-phenylhydrazono)butanoic Acid
(5a)
Benzoic hydrazide (660 mg, 4.85 mmol) was used. Recrystallization
from xylene gave yellow crystals.
Yield: 151 mg (96%); mp 234–235 °C.
IR (KBr): 3173, 3061, 2358, 1672, 1596, 1520, 1382 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.36 (s, 3 H), 7.06–7.13 (m, 1 H),
7.38–7.66 (m, 7 H), 7.93–8.00 (m, 2 H), 11.35 (s, 1 H), 13.31 (s, 1 H),
14.81 (s, 1 H).
All solvents were purchased from Merck or Panreac and all reagents
were purchased from Aldrich. 2-(2-Phenylhydrazono)butanoic acid
ethyl ester 2 was prepared according to a literature procedure.25 TLC
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

F
A. Kotali et al.
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Synthesis
13C NMR (100 MHz, DMSO-d6): δ = 13.3, 16.9, 115.4, 115.6, 123.2,
123.6, 124.4, 126.9, 128.7, 128.8, 128.9, 129.9, 130.0, 132.7, 133.0,
142.6, 143.4, 152.2, 157.1, 165.0, 165.6, 166.5.
3-[2-(2-Nitrobenzoyl)hydrazono]-2-(2-phenylhydrazono)butano-
ic Acid (5e)
2-Nitrobenzoic hydrazide (873 mg, 4.85 mmol) was used. Recrystalli-
zation from xylene gave orange crystals.
ESI-MS: m/z = 325 [M+ + 1].
Yield: 171 mg (95%); mp 247–248 °C.
IR (KBr): 3184, 3029, 2423, 1686, 1646, 1589, 1523 cm–1
Anal. Calcd for C17H16N4O3: C, 62.95; H, 4.97; N, 17.27. Found: C,
62.91; H, 4.79; N, 17.11.
.
1H NMR (400 MHz, DMSO-d6): δ = 2.27 (d, J = 5.8 Hz, 1 H), 2.34 (s, 2
H), 7.06–7.34 (m, 1 H), 7.37–7.47 (m, 4 H), 7.80–7.93 (m, 3 H), 8.22–
8.25 (m, 1 H), 11.86 (s, 1 H), 13.30 (s, 1 H), 14.76 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 13.3, 16.9, 115.1, 115.4, 115.7,
123.2, 123.5, 123.7, 124.5, 124.7, 126.8, 129.3, 129.8, 130.0, 130.5,
130.6, 130.8, 131.2, 131.9, 132.1, 134.7, 135.3, 142.6, 143.3, 147.1,
151.8, 156.5, 163.3, 165.4, 166.8.
3-[2-(4-Methylbenzoyl)hydrazono]-2-(2-phenylhydrazono)buta-
noic Acid (5b)
4-Toluic hydrazide (722 mg, 4.85 mmol) was used. Recrystallization
from xylene gave yellow crystals.
Yield: 150 mg (92%); mp 245–246 °C.
IR (KBr): 3198, 3015, 1665, 1602, 1523, 1479 cm–1
.
ESI-MS: m/z = 370 [M+ + 1].
1H NMR (400 MHz, DMSO-d6): δ = 2.40 (s, 3 H), 2.46 (s, 2 H) 7.05–7.13
(m, 1 H), 7.35–7.42 (m, 5 H), 7.47–7.52 (m, 1 H), 7.85–7.92 (m, 2 H),
11.38 (s, 1 H), 11.44 (br s, 1 H), 13.40 (s, 1 H), 14.93 (s, 1 H).
Anal. Calcd for C17H15N5O5: C, 55.28; H, 4.09; N, 18.96. Found: C,
55.13; H, 3.61; N, 18.95.
13C NMR (100 MHz, DMSO-d6): δ = 13.3, 16.8, 21.6, 26.1, 115.4, 115.6,
123.2, 123.5, 124.4, 126.9, 128.7, 128.8, 129.4, 129.7, 129.9, 130.0,
130.1, 130.2, 142.6, 142.8, 142.9, 143.5, 152.0, 156.8, 164.8, 165.2,
165.7, 166.5.
3-[2-(2-Furoyl)hydrazono]-2-(2-phenylhydrazono)butanoic Acid
(5f)
2-Furoic acid hydrazide (606 mg, 4.85 mmol) was used. Recrystalliza-
tion from xylene gave yellow crystals.
ESI-MS: m/z = 325 [M+ + 1].
Yield: 149 mg (98%); mp 221–222 °C.
IR (KBr): 3303, 3139, 2359, 1681, 1587, 1535, 1508, 1469 cm–1
Anal. Calcd for C18H18N4O3: C, 63.89; H, 5.36; N, 16.56. Found: C,
63.63; H, 5.22; N, 16.52.
.
1H NMR (400 MHz, DMSO-d6): δ = 2.36 (s, 1 H), 2.42 (s, 2 H), 6.73 (dd,
J = 3.4, 1.6 Hz, 1 H), 7.06–7.11 (m, 1 H), 7.36–7.50 (m, 5 H), 7.99–8.01
(m, 1 H), 11.34 (s, 1 H), 13.34 (s, 1 H), 14.78 (s, 1 H).
1H NMR (500 MHz, DMSO-d6, 105 °C): δ = 2.44 (s, 3 H), 6.71 (dd, J =
3.7, 1.7 Hz, 1 H), 7.05–7.18 (m, 1 H), 7.38–7.45 (m, 5 H), 7.91 (dd, J =
1.7, 0.7 Hz, 1 H), 10.95 (s, 1 H), 13.24 (s, 1 H), 14.39 (s, 1 H).
3-[2-(4-Chlorobenzoyl)hydrazono]-2-(2-phenylhydrazono)buta-
noic Acid (5c)
4-Chlorobenzoic hydrazide (822 mg, 4.85 mmol) was used. Recrystal-
lization from benzene gave yellow crystals.
Yield: 169 mg (97%); mp 249–250 °C.
IR (KBr): 3158, 3036, 2353, 1675, 1592, 1521, 1471 cm–1
.
13C NMR (100 MHz, DMSO-d6): δ = 13.3 16.9, 112.6, 112.7, 115.4,
115.6, 116.8, 123.2, 123.6, 124.4, 126.4, 126.9, 128.5, 129.2, 129.9,
142.7, 143.4, 146.1, 146.3, 146.9, 152.5, 155.6, 156.0, 157.4, 165.5,
166.4.
13C NMR (125 MHz, DMSO-d6, 105 °C): δ = 13.1, 112.4, 113.1, 115.7,
116.5, 124.4, 129.9, 137.8, 143.1, 146.6, 155.9, 157.5, 165.4.
1H NMR (400 MHz, DMSO-d6): δ = 2.45 (s, 3 H), 7.06–7.09 (m, 1 H),
7.37–7.46 (m, 4 H), 7.63 (d, J = 8.3 Hz, 2 H), 8.02 (d, J = 8.3 Hz, 2 H),
11.54 (s, 1 H), 13.40 (br s, 1 H), 14.89 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 12.9, 115.1, 122.6, 124.0, 128.5,
129.5, 130.1, 131.2, 137.0, 142.1, 156.7, 163.5, 165.1.
ESI-MS: m/z = 315 [M+ + 1].
ESI-MS: m/z = 359 [M+ + 1].
Anal. Calcd for C15H14N4O4: C, 57.32; H, 4.49; N, 17.89. Found: C,
57.50; H, 4.36; N, 17.63.
Anal. Calcd for C17H15ClN4O3: C, 56.91; H, 4.21; N, 15.62; Cl, 9.88.
Found: C, 56.80; H, 4.03; N, 15.59; Cl, 9.89.
Crystal structure data: C15H14N4O4, M = 314.30, orthorhombic, space
group Pbcn (No. 60), a = 27.8952(5) Å, b = 8.0804(2) Å, c = 13.1762(2)
Å, V = 2969.97(10) Å3, Z = 8, T = 290(2) K, Dcalc = 1.406 g∙cm–3, Cu Kα
radiation, 2θmax = 134.54°, 11251 reflections collected, 2650 reflec-
tions unique and 2403 reflections with I > 2σ(I). Final GooF = 1.068,
R1 = 0.0392 and wR2 = 0.1092 for 2403 reflections and 233 parame-
ters. CCDC 1469500 contains the supplementary crystallographic
data for this paper. The data can be obtained free of charge from The
3-[2-(4-Nitrobenzoyl)hydrazono]-2-(2-phenylhydrazono)butano-
ic Acid (5d)
4-Nitrobenzoic hydrazide (873 mg, 4.85 mmol) was used. Recrystalli-
zation from xylene gave yellow crystals.
Yield: 151 mg (96%); mp 245–246 °C.
IR (KBr): 3437, 3234, 3069, 2360, 1649, 1594, 1515, 1388 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.39 (s, 1 H), 2.47 (s, 2 H), 7.07–
7.14 (m, 1 H), 7.38–7.42 (m, 2 H), 7.47–7.51 (m, 2 H), 8.17 (d, J = 8.9
Hz, 2 H), 8.38 (d, J = 8.6 Hz, 2 H), 11.79 (s, 1 H), 13.37 (s, 1 H), 14.84 (s,
1 H).
Cambridge
www.ccdc.cam.ac.uk/getstructures.
Crystallographic
Data
Centre
via
Selected bond distances [Å]: C3–N4 = 1.371(2), N4–N5 = 1.372(2),
N5–C6 = 1.285(2), C6–C7 = 1.470(2), C7–N11 = 1.311(2), N11–N12 =
1.318(2).
13C NMR (100 MHz, DMSO-d6): δ = 13.0, 114.9, 115.2, 123.5, 124.1,
129.5, 129.8, 129.9, 142.1, 149.4, 155.5, 165.0.
2-(2-Phenylhydrazono)-3-[2-(thiophene-2-carbonyl)hydrazo-
no]butanoic Acid (5g)
ESI-MS: m/z = 370 [M+ + 1].
Anal. Calcd for C17H15N5O5: C, 55.28; H, 4.09; N, 18.96. Found: C,
55.61; H, 3.74; N, 18.91.
Thiophene-2-carboxylic acid hydrazide (683 mg, 4.85 mmol) was
used. Recrystallization from xylene gave yellow crystals.
Yield: 155 mg (97%); mp 225–227 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

G
A. Kotali et al.
Paper
Synthesis
IR (KBr): 3181, 3097, 2360, 1655, 1590, 1521, 1414 cm–1
.
4-Acetoxy-8-methyl-6-oxo-2-phenyl-7-(phenylhydrazono)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6a)
1H NMR (400 MHz, DMSO-d6): δ = 2.38 (s, 1 H), 2.45 (s, 2 H), 7.03–
7.11 (m, 1 H), 7.26–7.46 (m, 5 H), 7.95–8.12 (m, 2 H), 11.42 (s, 1 H),
13.36 (s, 1 H), 14.79 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 13.4, 17.0, 115.3, 115.6, 123.3,
123.5, 124.4, 126.9, 128.5, 129.2, 130.0, 131.1, 133.2, 136.9, 142.7,
143.4, 152.1, 156.9, 159.4, 165.5, 166.4.
Boric acid (191 mg, 3.08 mmol), Ac2O (126 mg, 12.32 mmol), and hy-
drazone 5a (500 mg, 1.54 mmol) were used. Purification via column
chromatography (PE/EtOAc, 5:1) gave yellow crystals.
Yield: 339 mg (56%); mp 198–200 °C (from CH2Cl2/PE).
IR (KBr): 3449, 3113, 1718, 1692, 1641, 1592, 1522 cm–1
.
ESI-MS: m/z = 331 [M+ + 1].
1H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.75 (s, 3 H), 7.27–7.28
(m, 1 H), 7.43–7.52 (m, 4 H), 7.57–7.59 (m, 1 H), 8.16 (d, J = 7.0 Hz, 2 H
), 14.17 (s, 1 H).
Anal. Calcd for C15H14N4O3S: C, 54.53; H, 4.27: N, 16.96; S, 9.68.
Found: C, 54.50; H, 4.07; N, 16.94; S, 9.89.
3-[2-(Phenylacetyl)hydrazono]-2-(2-phenylhydrazono)butanoic
Acid (5h)
13C NMR (100 MHz, CDCl3): δ = 13.9, 22.9, 116.6, 121.8, 126.7, 126.8,
128.6, 128.7, 129.8, 133.0, 141.0, 161.2, 163.0, 170.9, 172.6.
ESI-MS: m/z = 333 [M+ – 59].
Phenylacetic hydrazide (722 mg, 4.85 mmol) was used. Recrystalliza-
tion from xylene gave yellow crystals.
Anal. Calcd for C19H17BN4O5: C, 58.19; H, 4.37; N, 14.29. Found: C,
58.23; H, 4.23; N, 13.98.
Yield: 150 mg (92%); mp 221–222 °C.
IR (KBr): 3422, 3174, 3061, 2360, 1659, 1598, 1534, 1487 cm–1
.
4-Acetoxy-8-methyl-6-oxo-7-(phenylhydrazono)-2-(4-tolyl)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6b)
1H NMR (400 MHz, DMSO-d6): δ = 2.36 (s, 3 H), 3.79 (s, 2 H), 7.08 (t,
J = 7.2 Hz, 1 H), 7.25–7.44 (m, 9 H), 11.35 (s, 1 H), 13.31 (s, 1 H), 14.31
(s, 1 H).
Boric acid (183 mg, 2.96 mmol), Ac2O (121 mg, 11.84 mmol), and hy-
drazone 5b (500 mg, 1.48 mmol) were used. Purification via column
chromatography (PE/EtOAc, 5:1) gave yellow crystals.
13C NMR (100 MHz, DMSO-d6): δ = 13.0, 16.5, 40.5, 115.3, 115.5,
123.0, 123.5, 124.3, 126.7, 127.1, 128.6, 128.8, 128.9, 129.6, 129.7,
129.8, 129.9, 135.8, 136.0, 142.6, 143.4, 149.8, 154.4, 165.5, 166.5,
167.8, 168.5.
Yield: 354 mg (59%); mp 215–216 °C (from CHCl3/PE).
IR (KBr): 3425, 1712, 1684, 1643, 1583, 1528 cm–1
.
ESI-MS: m/z = 339 [M+ + 1].
1H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.45 (s, 3 H), 2.75 (s, 3 H),
7.26–7.28 (m, 1 H), 7.30 (d, J = 8.1 Hz, 2 H), 8.05 (d, J = 8.3 Hz, 2 H),
14.15 (s, 1 H).
Anal. Calcd for C18H18N4O3: C, 63.89; H, 5.36; N, 16.56. Found: C,
63.75; H, 5.25; H, 16.44.
3-(2-Acetylhydrazono)-2-(2-phenylhydrazono)butanoic Acid (5i)
13C NMR (100 MHz, CDCl3): δ = 13.8, 21.8, 22.9, 116.6, 121.8, 124.0,
126.6, 128.6, 129.4, 129.7, 141.0, 143.9, 161.2, 162.5, 171.1, 172.6.
ESI-MS: m/z = 347 [M+ – 59].
Acetyl hydrazide (345 mg, 4.85 mmol) was used. Recrystallization
from ethanol gave yellow crystals.
Yield: 971 mg (77%); mp 226–227 °C.
IR (KBr): 3421, 3136, 3012, 2359, 1700, 1632, 1589, 1520 cm–1
Anal. Calcd for C20H19BN4O5: C, 59.14; H, 4.71; N, 13.79. Found: C,
58.71; H, 4.61; N, 13.72.
.
1H NMR (400 MHz, DMSO-d6): δ = 2.08 (s, 3 H), 2.31 (s, 3 H), 7.09 (d,
J = 7.0 Hz, 1 H), 7.33–7.44 (m, 4 H), 11.13 (s, 1 H), 13.31 (s, 1 H), 14.86
(s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 12.1, 16.3, 21.4, 21.5, 115.2, 115.5,
123.0, 124.3, 126.8, 129.7, 129.8, 129.9, 142.7, 143.5, 148.9, 153.6,
165.6, 166.5, 166.9, 167.6.
4-Acetoxy-2-(4-chlorophenyl)-8-methyl-6-oxo-7-(phenylhydrazo-
no)-2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxaza-
borine (6c)
Boric acid (173 mg, 2.80 mmol), Ac2O (114 mg, 11.20 mmol), and hy-
drazone 5c (500 mg, 1.40 mmol) were used. Purification via column
chromatography (PE/EtOAc, 5:1) gave orange crystals.
ESI-MS: m/z = 263 [M+ + 1].
Yield: 327 mg (55%); mp 236–237 °C (from CH2Cl2/PE).
Anal. Calcd for C12H14N4O3: C, 54.96; H, 5.38; N, 21.36. Found: C,
54.88; H, 5.17; N, 21.33.
IR (KBr): 3421, 3092, 1712, 1677, 1638, 1591, 1522 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.76 (s, 3 H), 7.27–7.30
(m, 1 H), 7.44–7.49 (m, 6 H), 8.10 (d, J = 8.5 Hz, 2 H), 14.20 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 13.9, 22.8, 116.7, 121.7, 125.4, 126.8,
129.0, 129.7, 129.8, 139.4, 140.9, 161.1, 163.2, 170.0, 172.4.
ESI-MS: m/z = 367 [M+ – 59].
Boron Heterocycles 6; General Procedure
Boron triacetate was prepared first. Ac2O (8 mmol) was added to boric
acid (2 mmol). The mixture was then refluxed with stirring for 1 h.
Next, the reaction mixture was allowed to reach r.t. and at that point
hydrazone 5 (1 mmol) was added. Subsequently, the reaction mixture
was heated under reflux and stirring for 2 h. The reaction mixture
was allowed to reach r.t. and then it was poured into a mixture of ice
(10 mL) and H2O (20 mL) with stirring. The resulting precipitate was
collected by filtration, washed with H2O to pH 7, and finally with Et2O
(10 mL), to give solid products, which were subjected to column chro-
matography and recrystallized to afford pure products 6.
Anal. Calcd for C19H16BClN4O5: C, 53.49; H, 3.78; N, 13.13; Cl, 8.31.
Found: C, 53.34; H, 3.65; N, 13.05; Cl, 8.60.
4-Acetoxy-8-methyl-2-(4-nitrophenyl)-6-oxo-7-(phenylhydrazo-
no)-2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxaza-
borine (6d)
Boric acid (168 mg, 2.70 mmol), Ac2O (110 mg, 10.80 mmol), and hy-
drazone 5d (500 mg, 1.35 mmol) were used. Purification via column
chromatography (PE/EtOAc, 3:1) gave orange crystals.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

H
A. Kotali et al.
Paper
Synthesis
Yield: 373 mg (63%); mp 237–239 °C.
IR (KBr): 3422, 3128, 1725, 1674, 1641, 1594, 1523 cm–1
1H NMR (400 MHz, CDCl3): δ = 2.01 (s, 3 H), 2.80 (s, 3 H), 7.28–7.33
(m, 1 H), 7.46–7.51 (m, 4 H), 8.34 (d, J = 1.0 Hz, 4 H), 14.31 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 14.1, 22.8, 116.9, 121.5, 123.8, 127.2,
tallographic data for this paper. The data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
.
Selected bond distances [Å]: B1–O9 = 1.455(2), B1–O20 = 1.458(2),
B1–O2 = 1.461(2), B1–N5 = 1.548(2), C3–N4 = 1.305(2), N4–N5 =
1.405(2), N5–C6 = 1.298(2), C6–C7 = 1.446(2), C7–N11 = 1.321(2),
129.5, 129.9, 132.7, 140.7, 150.3, 161.0, 164.7, 168.7, 172.5.
ESI-MS: m/z = 378 [M+ – 59].
N11–N12
105.83(14), O9–B1–O2 = 114.12(14), O20–B1–O2 = 114.12(14), O9–
B1–N5 108.27(13), O20–B1–N5 115.22(15), O2–B1–N5
98.71(13).
= 1.295(2). Selected bond angles [°]: O9–B1–O20 =
=
=
=
Anal. Calcd for C19H16BN5O7: C, 52.20; H, 3.69; N, 16.02. Found: C,
51.84; H, 3.47; N, 15.87.
4-Acetoxy-8-methyl-6-oxo-7-(phenylhydrazono)-2-(2-thienyl)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6g)
4-Acetoxy-8-methyl-2-(2-nitrophenyl)-6-oxo-7-(phenylhydrazo-
no)-2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxaza-
borine (6e)
Boric acid (187 mg, 3.02 mmol), Ac2O (124 mg, 12.08 mmol), and hy-
drazone 5g (500 mg, 1.51 mmol) were used. Purification via column
chromatography (PE/EtOAc, 3:1) gave orange crystals.
Boric acid (168 mg, 2.70 mmol), Ac2O (110 mg, 10.80 mmol), and hy-
drazone 5e (500 mg, 1.35 mmol) were used. The solid was washed
with Et2O to give the pure derivative 6e. Alternatively, purification via
column chromatography (PE/EtOAc, 3:1) gave orange crystals.
Yield: 350 mg (58%); mp 206–207 °C (from CH2Cl2/PE).
IR (KBr): 3433, 3103, 1723, 1681, 1643, 1593, 1526 cm–1
.
Yield: 491 mg (83%); mp 235–236 °C.
IR (KBr): 3421, 3132, 1720, 1691, 1639, 1596, 1529 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.01 (s, 3 H), 2.73 (s, 3 H), 7.17–7.20
(m, 1 H), 7.26–7.28 (m, 1 H), 7.43–7.48 (m, 4 H), 7.64 (d, J = 4.0 Hz, 1
H), 7.92 (d, J = 2.8 Hz, 1 H), 14.14 (s, 1 H).
1H NMR (400 MHz, CDCl3): δ = 1.99 (s, 3 H), 2.69 (s, 3 H), 7.25–7.28
(m, 1 H), 7.42–7.48 (m, 4 H), 7.68–7.70 (m, 2 H), 7.81–7.82 (m, 1 H),
8.04–8.06 (m, 1 H), 14.26 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 13.9, 22.9, 116.6, 121.7, 126.7, 128.3,
13C NMR (100 MHz, CDCl3): δ = 14.1, 22.8, 116.8, 121.3, 121.4, 123.9,
127.2, 129.8, 131.2, 132.2, 132.8, 140.7, 149.5, 160.9, 165.0, 168.0,
172.4.
129.3, 129.8, 132.6, 133.1, 140.9, 161.1, 162.5, 167.0, 172.6.
ESI-MS: m/z = 339 [M+ – 59].
Anal. Calcd For C19H16BN4O5S: C, 51.28; H, 3.80; N, 14.07; S, 8.03.
Found: C, 51.38; H, 3.80; N, 13.93; S, 7.95.
ESI-MS: m/z = 378 [M+ – 59].
Anal. Calcd for C19H16BN5O7·0.2H2O: C, 51.77; H, 3.75; N, 15.89.
Found: C, 51.78; H, 3.34; N, 15.71.
4-Acetoxy-2-benzyl-8-methyl-6-oxo-7-(phenylhydrazono)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6h)
4-Acetoxy-2-(2-furyl)-8-methyl-6-oxo-7-(phenylhydrazono)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6f)
Boric acid (183 mg, 2.96 mmol), Ac2O (121 mg, 11.84 mmol), and hy-
drazone 5h (500 mg, 1.48 mmol) were used. Purification via column
chromatography (PE/EtOAc, 3:1) gave yellow crystals.
Boric acid (197 mg, 3.20 mmol), Ac2O (130 mg, 12.80 mmol), and hy-
drazone 5f (500 mg, 1.60 mmol) were used. Purification via column
chromatography (PE/EtOAc, 2:1) gave orange crystals.
Yield: 330 mg (55%); mp 158–160 °C (from CHCl3/PE).
IR (KBr): 3418, 3118, 1715, 1684, 1640, 1594, 1460 cm–1
.
Yield: 530 mg (87%); mp 184–185 °C (from CH2Cl2/PE).
1H NMR (400 MHz, CDCl3): δ = 1.99 (s, 3 H), 2.66 (s, 3 H), 3.87 (s, 2 H),
7.25–7.45 (m, 10 H), 14.15 (s, 1 H).
IR (KBr): 3129, 1654, 1594, 1521, 1461 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 1.91 (s, 3 H), 2.67 (s, 3 H), 6.80 (dd,
J = 3.5, 1.5 Hz, 1 H), 7.27 (t, J = 7.4 Hz, 1 H), 7.44–7.48 (m, 3 H), 7.70 (d,
J = 7.8 Hz, 2 H), 8.10 (d, J = 1.0 Hz, 1 H), 13.70 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 14.5, 23.0, 113.4, 116.9, 117.4,
118.9, 121.8, 126.8, 130.1, 141.7, 142.0, 148.9, 159.8, 162.0, 171.6.
11B NMR (160 MHz, CDCl3): δ = 3.64.
ESI-MS: m/z = 323 [M+ – 59].
13C NMR (100 MHz, CDCl3): δ = 14.0, 22.9, 36.0, 116.6, 121.4, 126.7,
127.4, 128.7, 129.3, 129.8, 133.6, 140.9, 161.0, 163.6.8, 172.5, 175.2.
ESI-MS: m/z = 347 [M+ – 59].
Anal. Calcd for C20H19 BN4O5: C, 59.14; H, 4.71; N, 13.79. Found: C,
59.02; H, 4.71; N, 13.67.
4-Acetoxy-2,8-dimethyl-6-oxo-7-(phenylhydrazono)-
2H,4H,6H,7H,8H-[1,3,4,2]oxadiazaborolo[2,3-b][1,3,2]oxazaborine
(6i)
Anal. Calcd for C17H15BN4O6: C, 53.43; H, 3.96; N, 14.66. Found: C,
52.89; H, 3.63; N, 14.61.
Boric acid (236 mg, 3.82 mmol), Ac2O (156 mg, 15.28 mmol), and hy-
drazone 5i (500 mg, 1.91 mmol) were used. Purification via column
chromatography (PE/EtOAc, 3:1) gave yellow crystals.
Crystal structure data: C17H15BN4O6·CHCl3, M = 501.51, triclinic, space
group P–1 (No. 2), a = 10.3247(5) Å, b = 10.4227(5) Å, c = 12.5175(8)
Å, α = 75.919(5)°, β = 68.422(5)°, γ = 65.179(5)°, V = 1128.41(11) Å3 , Z
= 2, T = 290(2) K, Dcalc = 1.476 g∙cm–3 , Cu Kα radiation, 2θmax = 134.56°,
17605 reflections collected, 4035 reflections unique and 3440 reflec-
tions with I > 2σ(I). Final GooF = 1.036, R1 = 0.0435 and wR2 = 0.1225
for 3440 reflections and 337 parameters. During refinement, three Cl
atoms were found to be disordered over two sites with occupancies of
0.65(2) and 0.35(2). CCDC 1469499 contains the supplementary crys-
Yield: 385 mg (61%); mp 208–209 °C.
IR (KBr): 3438, 3128, 1707, 1678, 1646, 1592, 1562 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.27 (s, 3 H), 2.66 (s, 3 H),
7.26–7.28 (m, 1 H), 7.44–7.46 (m, 4 H), 14.14 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 13.9, 15.6, 22.9, 116.6, 121.3, 126.7,
129.8, 140.9, 161.1, 161.2, 172.5, 174.3.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

I
A. Kotali et al.
Paper
Synthesis
ESI-MS: m/z = 271 [M+ – 59].
(15) Dandawate, P.; Khan, E.; Padhye, S.; Gaba, H.; Sinha, S.;
Deshpande, J.; Swamy, K. V.; Khetmalas, M.; Ahmad, A.; Sarkar,
F. H. Bioorg. Med. Chem. Lett. 2012, 22, 3104.
Anal. Calcd for C14H15 BN4O5: C, 50.94; H, 4.58; N, 16.97. Found: C,
50.88; H, 4.35; N, 17.06.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I