Synthesis of novel dehydroacetic acid N-aroylhydrazone-derived boron heterocycles

Article abstract of DOI:10.1016/j.tet.2015.03.097

Abstract The synthesis of new boron heterocycles is reported via the reaction of dehydroacetic acid N-aroylhydrazones with boron acetate. The procedure involves formation of new zwitterionic, tetrahedral boron structures.

Full text of DOI:10.1016/j.tet.2015.03.097

Tetrahedron xxx (2015) 1e5
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of novel dehydroacetic acid N-aroylhydrazone-derived
boron heterocycles
,
a
a
a
b
Antigoni Kotali a , Fani Dimoulaki , Elvira Kotali , Anna Maniadaki , Philip A. Harris ,
*
Ewa Rozycka-Soko1owska , Piotr Ba1czewski d, John A. Joule e
c
c,
ꢀ_
a Laboratory of Organic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
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 Cze˛stochowa, 42-201 Cze˛stochowa, Poland
d
ꢀ ꢀ
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 90-363 Łodz, Poland
e The School of Chemistry, The University of Manchester, Manchester M13 9PL, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of new boron heterocycles is reported via the reaction of dehydroacetic acid N-aroylhy-
drazones with boron acetate. The procedure involves formation of new zwitterionic, tetrahedral boron
structures.
Received 11 January 2015
Received in revised form 15 March 2015
Accepted 26 March 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Dedicated to the memoryof Alan R. Katritzky,
an invaluable mentor, friend, and scientific
collaborator over the last 25 years
Keywords:
Dehydroacetic acid
N-Acylhydrazones
Boron acetate
[1,3,4,2]Oxadiazaborol[2,3-b][3,4-e]pyrano
[1,3,2]-oxazaborines
1. Introduction
electrophiles and Lewis acids. Thus, trivalent boron compounds can
readily form stable dative bonds with nucleophiles transforming
Boron is an interesting element that has attracted the attention
of the scientific community regarding its chemistry, pharmacology,
and toxicology and it is considered to be widely useful in future
drug discovery.1,2 It commonly exists in nature as boric acid and is
an essential plant nutrient acting in the cell walls to bind poly-
saccharides.3 Although it is available to cells, there are very few
known natural products containing boron. The first natural product
found to contain boron was boromycin4 (Fig. 1) a polyether mac-
rolide antibiotic active against Gram-positive bacteria5 that was
shown to also have anti-HIV activity.6 Another interesting boron-
containing natural product is a hydrated boric acid complex with
a tetrahydroxy-dihydrofuran, known as AI-2, which is a bacterial
autoinducer involved in quorum sensing.7 Trivalent boron com-
pounds have an empty p-orbital, which makes them strong
from an uncharged, trigonal planar structure to an anionic tetra-
hedral structure. In a similar way it forms bonds with nucleophiles
in enzyme active sites. The use of boron in small-molecule phar-
maceuticals is increasing and this has been recently exemplified by
the one boron-containing compound on the market, VelcadeÒ
(bortezomib) approved by the FDA and acting as a proteasome in-
hibitor, whereas several other boron derivatives have been tested in
clinical trials.1,2,8,9
3-Acetyl-4-hydroxy-6-methyl-2-oxo-2H-pyran, which is also
known as dehydroacetic acid (DHA) is a versatile starting material
for the synthesis of a wide variety of heterocyclic ring systems. DHA
derivatives have been reported to bind to DNA.10 Moreover, various
analogs of 4-hydroxypyran-2-ones have been reported to inhibit
HIV protease, one of the crucial key enzymes essential for the
replication of HIV.11,12 Having this in mind we thought that het-
erocycles, which contain a boron atom in their backbone, in addi-
tion to the pyrone ring of DHA, might exhibit interesting biological
activities.
* Corresponding author. Tel./fax: þ30 2310996253; e-mail address: kotali@eng.
auth.gr (A. Kotali).
http://dx.doi.org/10.1016/j.tet.2015.03.097
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
A. Kotali et al. / Tetrahedron xxx (2015) 1e5
According to our knowledge, no synthetic analogs have been re-
ported in the literature and having in mind that it is well known
that boron readily forms bimetallic complexes,22e28 we now report
the synthesis of zwitterionic tetrahedral boron derivatives 6aeg.
2. Results and discussion
Dehydroacetic acid N-aroylhydrazones 3 were synthesized via
treatment of commercially available dehydroacetic acid 1 with the
appropriate hydrazide 2 in methanol, as depicted in Scheme 1,
according to literature methods.29
The molar ratio of the reactants was 1:1 and the reaction was
performed under reflux for 2 h, to yield hydrazones 3aeg in ex-
cellent yields (96e99%). Hydrazones 3 were subsequently treated
with boron acetate (strictly ‘acetic acid, anhydride with boric acid’)
generated in situ, via the reaction of boric acid 4 with acetic an-
hydride 5. The reactions were performed under reflux to form the
desired products 6 in good yields, 66e84%. The reaction conditions,
the yields of formation of the new compounds 6 as well as their
melting points are presented in Table 1.
Table 1
,
Substituted oxadiazaborol-pyrano-oxazaborines 6aeg produced via Scheme 1a,b
Fig. 1. Boron derivatives with biological activity.
Comp.
R
Reagents
Ratio of reactants
Yield %
6a
6b
6c
6d
6e
6f
Ph
3aþ4þ5
3bþ4þ5
3cþ4þ5
3þ4þ5
1/2/8
1/2/8
1/2/8
1/2/8
1/2/8
1/2/8
1/2/8
81
82
74
66
80
68
84
Moreover, hydrazones are very well known both for their bi-
p-H3CC6H4
p-ClC6H4
p-O2NC6H4
o-O2NC6H4
2-Furyl
ological activities12e15 as well as for their use as starting materials
in organic synthesis.16e20 Hydrazone derivatives have been re-
ported to possess anticonvulsant, antidepressant, analgesic, anti-
inflammatory, antiplatelet, antimalarial, antimicrobial, anti-
mycobacterial, antitumoral, vasodilator, antiviral, and anti-
schistosomiasis activities.13 Furthermore, 4-pyrimidone hydrazone
derivatives exhibit excellent activity against wild-type HIV-1,14
whereas fluorescein and bis-daunomycin hydrazone derivatives
are characteristic examples of hydrazones that have been reported
to interact with DNA.12,15
3dþ4þ5
3eþ4þ5
3fþ4þ5
6g
2-Thienyl
a
All reactions conducted in refluxing acetic anhydride for 3 h.
Products 6aeg were recrystallized from EtOH.
b
The desired boron heterocycles
6 were purified via re-
crystallization from ethanol. Products 6aeg are new compounds
and their structures were established by their IR, 1H, 13C NMR, and
mass spectra as well as by their elemental analyses. Additionally, an
X-ray crystal analysis was carried out for one of the examples, 6a.
In the IR spectra of 6, characteristic absorptions appeared at
3427e3443 (for B/N bond), 3149e3094 (for ]CeH and CeH
bonds), 1721e1728 (for ester C]O), 1631e1492 (for C]C bonds,
Based on the above literature information and on our continuing
interest in hydrazono substrates21 we designed the synthesis of
novel pyranone-fused boron heterocycles of type 6 (Scheme 1).
lactone C]O, and C]N bonds) cmꢀ1
.
In the 1H NMR spectra of the new boron compounds 6, there
were two characteristic three-proton singlets in the ranges
1.85e1.97 and 2.34e2.37 ppm, assigned to the protons of the
methyl at C-5 (see numbering in Fig. 2) on the pyrone ring and at C-
1 of the oxazaborine ring. A third characteristic singlet, due the
methyl protons of an acetoxy group appeared at 2.79e2.93 ppm.
Fig. 2. View of 6a, showing the tetrahedral environment around the boron atom, the
atom numbering scheme, and the CeH/N intramolecular hydrogen bond (red dashed
line) forming a pattern with the S(5) descriptor. Displacement ellipsoids are drawn at
the 30% probability level, and H atoms are drawn as spheres of arbitrary radii.
Scheme 1. Synthesis of boron heterocycles 6.
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A. Kotali et al. / Tetrahedron xxx (2015) 1e5
3
The signals for protons at C-6 (see numbering in Fig. 2) of the
pyrone ring appeared at 6.16e6.57 ppm.
the R22ð18Þ ring. There are no direction-specific interactions be-
tween molecules belonging to adjacent chains.
In the 13C NMR spectra of compounds 6, characteristic reso-
nances appeared at 16.2e21.8 ppm that we assign to the two
methyl carbons located on the ring system; the methyl carbons
of the acetoxy groups gave signals in the range 22.7e22.9 ppm.
The signals at lowest field, in the ranges 170.3e171.0 and
171.2e172.5 ppm, are assigned to C-4 of the pyrone ring and the
carbonyl carbon of the acetoxy group, respectively. In the cases of
boron heterocycles 6c (R¼p-ClC6H4) and 6d (R¼p-O2NC6H4) only,
where both 1H and 13C NMR spectra were obtained in DMSO-d6,
there was evidence for the existence of two stereoisomers, with
Currently, we are only in a position to speculate on the order of
events that lead to structures 6. We suggest that the first step is
displacement of acetate from the boron by the phenolic hydroxyl,
via a tetravalent boronate, producing 7. Intramolecular interaction
between the imine nitrogen and the boron, with loss of acetate
would then generate iminium ion 8. This could now suffer intra-
molecular attack by the amide carbonyl oxygen with loss of acetic
acid, forming 9. Finally, the system would be rendered neutral by
addition of acetate to the boron forming 6 (Scheme 2).
respect to the tetracoordinated boron atom. Specifically, in the 13
C
NMR spectra there were two signals for each of the two types of
methyl, two ester carbonyl carbon signals, and two peaks for C-4 of
the pyrone ring. By signal integration, it seemed that the stereo-
isomers were present in ratios of 9:1 and 11.5:1 for 6c and 6d,
respectively. However, in the 1H NMR of these two substances, only
peaks for the major product were observable, the signals for the
minor stereoisomer appearing only in traces.
Finally, boron derivatives 6 showed prominent peaks corre-
sponding to the ions [Mþ23] or [Mꢀ59] in their mass spectra and
these were assigned to [MþNa] and [MꢀOCOCH3], respectively.
An X-ray diffraction analysis was carried out on boron compound
6a. The structure that was found by X-ray crystallography is shown
in Fig. 2. The boron atom is in a distorted tetrahedral environment
with three oxygen atoms and one nitrogen atom as coordinating
atoms (Fig. 2). Coordination angles lie in the range from 99.2(1)ꢁ to
115.7(1)ꢁ and lead to an angle variance30 of 45.44(deg).2 The three
BeO bonds are of the same length, and are shorter than the BeN
distance. As can be seen in Fig. 2, there is one weak intramolecular
CeH/N hydrogen bond (Table 2), which links methyl atom C2, via
H2B, with atom N1, and generates an S(5) graph-set motif.31
Scheme 2. Mechanism of formation of derivatives 6.
3. Conclusion
In conclusion, we have presented a convenient and general
method for the straightforward preparation of novel boron de-
rivatives in very good yields. The novel boron heterocycles could
possibly serve as useful bioactive scaffolds since they combine bi-
ological features in their structure, specifically: (i) the bioactive
anionic tetrahedral boron structure, (ii) a bioactive dehydroacetic
unit as well as the bioactive hydrazonic part (C]NeNe).
Table 2
Hydrogen-bond geometry
DeH/A [ꢁ]
ꢁ
ꢁ
ꢁ
DeH/A
DeH [A]
H/A [A]
D/A [A]
C2eH2B/N1
C6eH6/O4(i)
C13eH13/O5(ii)
0.98(2)
0.93
2.49(2)
2.59
2.884(2)
3.483(2)
3.302(2)
104(2)
162
142
0.93
2.52
Symmetry codes: (i) ꢀx, 2ꢀy, 1ꢀz; (ii) 1ꢀx, 1ꢀy, 2ꢀz.
4. Experimental section
4.1. General
The crystal structure of 6a contains two weak, non-conventional
CeH/O hydrogen bonds (Table 2), which together result in the for-
mation of a one-dimensional framework in the form of a continuous
molecular chain (Fig. 3). The first of these is from the C6 atom of the
molecule at (x, y, z) via H6 to the O4 atom of the acetoxy group be-
longing to the molecule at (ꢀx,2ꢀy,1ꢀz), and forms the ring with the
R22ð12Þ descriptor. The second, that is, the CeH/O intermolecular
interaction between the aromatic atoms C13eH13 of the molecule at
(x, y, z) and the acetoxy group (atom O5) at (1ꢀx,1ꢀy,2ꢀz), generates
All solvents were purchased from Merck or Panreac and all re-
agents were purchased from Aldrich. Compounds 3 were prepared
according to the literature procedure.29 TLC plates were Merck
plastic plates with silica gel 60F254 (70e230 mesh). Melting points
were recorded by a Fischer Scientific melting point measurement
apparatus. IR spectra were recorded on an FTIR Nicolet 200 spec-
trometer. 1H (400 MHz) and 13C (100 MHz) NMR spectra were
recorded on a Bruker Avance 400 instrument and the chemical
shifts are reported in
d (ppm) values relative to either CDCl3,
(d
¼7.30 and 77.0 ppm for 1H and 13C NMR, respectively, for CDCl3)
or DMSO-d6
(d
¼2.50 and 39.5 ppm for 1H and 13C NMR, re-
spectively, for DMSO-d6). Coupling constants are reported in hertz
(Hz). MS were measured on a Platform II spectrometer.
4.2. Procedure for the synthesis of 3-[1-(acyl-hydrazono)-
ethyl]-4-hydroxy-2H-1-benzopyran-2-ones (6)
According to the literature,29 the appropriate hydrazide (2,
1 mmol) was added to a solution of dehydroacetic acid 1 (1 mmol)
in methanol (15e20 mL). The mixture was refluxed for 2 h and
Fig. 3. Part of the crystal structure of 6a, showing the one-dimensional chain and
supramolecular motifs formed by two CeH/O hydrogen bonds (pink and blue dashed
lines). H atoms not involved in these interactions have been omitted for clarity.
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4
A. Kotali et al. / Tetrahedron xxx (2015) 1e5
cooled to rt. The resulting precipitate was collected by filtration and
dried in vacuum to afford pure dehydroacetic acid N-acylhy-
drazones (3aeg) as solids in very good yields.
retrieving.html or from the Cambridge Crystallographic Data
Centre.
4.3.2. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(p-toluic)-8H,10H,12H-
[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-oxazaborine
(6b). Yellow needles (82%), mp 194e195 ꢁC; IR (KBr): 3440, 2921,
4.3. Reaction of N-acylhydrazones 3 with boron acetate
Boron acetate was prepared as follows: to boric acid 4 was
added acetic anhydride 5. The molar ratios of boric acid/acetic
anhydride and the reaction times are presented in Table 1. The
mixture was then refluxed with stirring for 1 h. Then the reaction
mixture was allowed to reach rt and at that point hydrazone 3 was
added. Subsequently, the reaction mixture was heated under reflux
and stirring for 2 h. The reaction mixture was allowed to reach rt
and then it was poured into a mixture ice (10 mL) and H2O (20 mL)
and was stirred with a rod. The resulting precipitate was filtered off,
washed with H2O to pH¼7 and finally with Et2O (10 mL) to give
solid products, which were recrystallized from EtOH to afford pure
products 6 (Table 1).
1728, 1632, 1538, 1537 cmꢀ1. 1H NMR (CDCl3, 400 MHz):
d 1.94 (s,
3H), 2.34 (s, 3H), 2.42 (s, 3H), 2.90 (s, 1H), 6.16 (s, 1H), 7.27 (d,
J¼8.6 Hz, 2H), 8.02 (d, J¼8.1 Hz, 1H) ppm; 13C NMR (CDCl3,
100 MHz):
d 16.47, 20.70, 21.77, 22.71, 99.9, 102.3, 124.0, 128.4,
129.3, 143.6, 160.7, 160.8, 168.6, 169.0, 170.3, 171.1 ppm; MS (ESIþ):
m/z 389 (Mþ23), 309 (Mꢀ59). Anal. Calcd for C18H17BN2O6: C,
58.72; H, 4.65; N, 7.61. Found: C, 58.45; H, 4.44; N, 7.52.
4.3.3. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(p-chlorophenyl)-
8H,10H,12H-[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-ox-
azaborine (6c). Yellow needles (74%), mp 242e243 ꢁC; IR (KBr):
3443, 3098, 1726, 1632, 1585, 1536 cmꢀ1
.
1H NMR (DMSO-d6,
400 MHz) for the major product:
d 1.85 (s, 3H), 2.35 (s, 3H), 2.79 (s,
4.3.1. 4-Acetoxy-8,12-dimethyl-10-oxo-2-phenyl-8H,10H,12H-
[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-oxazaborine
(6a). Yellow needles (81%), mp 192e193 ꢁC; IR (KBr): 3437, 3098,
1H), 6.53 (s, 1H), 7.64 (d, J¼8.6 Hz, 2H), 8.03 (d, J¼8.6 Hz, 1H) ppm;
13C NMR (DMSO-d6, 100 MHz) for the mixture of two isomers in
ratio 1/3:
d 16.2, 16.7, 20.4, 20.6, 21.5, 22.9, 99.1, 99.9, 102.2, 102.7,
1731, 1631, 1535, 1498 cmꢀ1
.
1H NMR (CDCl3, 400 MHz):
d
1.96
125.7, 126.6, 129.6, 129.7, 129.9, 130.0, 138.0, 138.3, 159.3, 160.5,
161.1, 162.4, 164.8, 166.8, 167.3, 168.9, 170.4, 170.7, 170.8, 172.5 ppm;
MS (ESIþ): m/z 411 (Mþ23), 329 (Mꢀ59). Anal. Calcd for
(s, 3H), 2.37 (s, 3H), 2.93 (s, 1H), 6.18 (s, 1H), 7.46e7.50 (m, 2H),
7.56e7.59 (m, 1H), 8.14e8.16 (m, 2H) ppm; 13C NMR (CDCl3,
100 MHz):
d
16.5, 20.7, 22.7, 99.9, 102.2, 126.8, 128.3, 129.5, 133.5,
C17H14BClN2O6$0.3H2O: C, 51.83; H, 3.74; N, 7.11; Cl, 9.00. Found: C,
160.5, 162.3, 167.7, 170.3, 170.6, 172.5 ppm; MS (ESIþ): m/z 377
(Mþ23), 295 (Mꢀ59). Anal. Calcd for C17H15BN2O: C, 57.66; H, 4.27;
N, 7.91. Found: C, 57.64; H, 4.22; N, 7.92.
51.89; H, 3.48; N, 6.90; Cl, 9.47.
4.3.4. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(p-nitrophenyl)-
8H,10H,12H-[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-ox-
azaborine (6d). Yellow needles (66%), mp 223e225 ꢁC; IR (KBr):
3440, 3094, 2357, 1722, 1632, 1547, 1518 cmꢀ1. 1H NMR (DMSO-d6,
4.3.1.1. Crystal structure determination. Data were collected on
an XCALIBURÔ3 CCD diffractometer. Radiation type: Cu
Ka
ꢁ
(wavelength: 1.54184 A); Temperature: 293(2) K; No. of measured,
independent and observed [I>2 (I)] reflections: 12,630, 3018, and
400 MHz) for the major product: d 1.86 (s, 3H), 2.37 (s, 3H), 2.83
s
(s, 3H), 6.57 (s,1H), 8.27 (d, J¼9.1 Hz, 2H), 8.39 (d, J¼9.3 Hz, 2H) ppm;
2758; R(int)¼0.024. The structure was solved by direct methods
and refined by full-matrix least-squares on F2 using the SHELX-97
program package.32 The non-hydrogen atoms were refined aniso-
tropically. The hydrogen atoms were first localized in difference
Fourier maps. The H2A, H2B, and H2C atoms of methyl group were
refined isotropically, and all other H atoms were treated as riding
atoms in geometrically idealized positions, with CeH distances of
0.93 ðCsp2 Þ and 0.97 ðCsp3 Þ; and with UisoðHÞ ¼ 1:2UeqðCsp2 Þ and
13C NMR (DMSO-d6,100 MHz) for the mixture of two isomers in ratio
1/3: d 16.3,16.9, 20.4, 20.65, 21.5, 22.9, 99.2,100.0,102.2,102.7,124.6,
124.7,129.5,129.6,132.6,133.5,150.2,150.3,160.4,160.6,161.0,164.0,
165.9, 166.4, 169.3, 170.6, 170.7, 171.0, 171.2, 172.5 ppm; MS (ESIþ):
m/z 422 (Mþ23), 340 (Mꢀ59). Anal. Calcd for C17H14BN3O8$0.15H2O:
C, 50.82; H, 3.59; N, 10.46. Found: C, 50.82; H, 3.13; N, 10.46.
4.3.5. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(o-nitrophenyl)-
8H,10H,12H-[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-ox-
azaborine (6e). Yellow needles (80%), mp 200e201 ꢁC; IR (KBr):
3427, 3100, 1728, 1638, 1546, 1492 cmꢀ1. 1H NMR (CDCl3, 400 MHz):
1:5UeqðCsp3 Þ: R[F2>2
s
(F2)]¼0.037; wR(F2)¼0.1062 and S¼1.044 for
3010 unique reflections and 250 parameters. Crystal data:
C
17H15BN2O6, M¼354.12; crystal system: triclinic; space group: P1;
ꢁ ꢁ ꢁ
3
a¼9.0258(4) A, b¼10.6867(5) A, c¼10.8761(5) A,
a
¼62.231(5)ꢁ,
d
1.97 (s, 3H), 2.37 (s, 3H), 2.88 (s, 3H), 2.90 (s, 1H), 6.19 (s, 1H),
7.71e7.75 (m, 2H), 7.87e7.89 (m, 1H); 8.07e8.09 (m, 1H) ppm; 13
NMR (CDCl3, 100 MHz): 16.7, 20.8, 22.7, 99.8, 102.3, 122.1, 124.0,
ꢁ
ꢁ
b
¼68.857(4)ꢁ, and
g
¼69.293(4) ; V¼843.60(7) A ; Z¼2 molecules
C
per unit cell; Dc¼1.394 g/cm3; crystal size 0ꢁ.41ꢂ0.17ꢂ0.15 mm.
d
ꢁ
Selected bond distances (A) and angles ( ):
131.5, 132.4, 132.5, 149.0, 160.4, 163.4, 166.5, 169.5, 170.7, 171.3 ppm;
MS (ESIþ): m/z 422 (Mþ23), 340 (Mꢀ59). Anal. Calcd for
B1eO3¼1.460(2),
B1eN2¼1.541(2),
N1eN2¼1.403(2),
B1eO3¼1.460(2),
C1eC3¼1.445(2),
O6eC11¼1.342(2),
O4eC9¼1.340(2),
C3eC7¼1.402(2),
C7eC6¼1.409(2),
O2eC4¼1.392(2),
C4eC3¼1.444(2),
B1eO4¼1.459(3),
N1eC11¼1.307(2),
C1eC2¼1.488(2),
O5eC9¼1.202(2),
C6eC5¼1.341(2),
C4eO1¼1.203(2),
B1eO6¼1.456(2),
N2eC1¼1.305(2),
O3eC7¼1.328(2),
C9eC10¼1.489(3),
C5eO2¼1.358(2),
C11eC12¼1.462(2),
C17H14BN3O8: C, 51.16; H, 3.54; N, 10.53. Found: C, 50.99; H, 3.42; N,
10.42.
4.3.6. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(2׳-furyl)-8H,10H,12H-
[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-oxazaborine
(6f). Yellow needles (68%), mp 209e210 ꢁC; IR (KBr): 3441, 3149,
2354,1724,1643,1534,1498 cmꢀ1. 1H NMR (CDCl3, 400 MHz):
d 1.95
(s, 3H), 2.36 (s, 3H), 2.91 (s, 1H), 6.16 (s, 1H), 6.59 (dd, J¼3.5, 1.8 Hz,
1H), 7.29 (d, J¼4.8 Hz, 1H); 7.66 (d, J¼1.0 Hz, 1H) ppm; 13C NMR
(CDCl3, 100 MHz):
d 16.5, 20.7, 22.7, 99.9, 102.3, 124.0, 128.4, 129.3,
143.6, 160.7, 160.8, 168.65, 169.0, 170.3, 171.1 ppm; MS (ESIþ): m/z
367 (Mþ23), 285 (Mꢀ59). Anal. Calcd for C15H13BN2O7: C, 52.36; H,
3.81; N, 8.14. Found: C, 52.45; H, 3.75; N, 8.1.4.
O3eB1eO4¼104.6(1), O3eB1eN2¼108.0(1), O3eB1eO6¼115.0(1),
O4eB1eO6¼114.5(1), O4eB1eN2¼115.7(1), O6eB1eN2¼99.2(1).
Full crystallographic data are contained in CCDC no. 1041538,
and can be obtained free of charge at www.ccdc.cam.ac.uk/conts/
4.3.7. 4-Acetoxy-8,12-dimethyl-10-oxo-2-(2׳-thienyl)-8H,10H,12H-
[1,3,4,2]oxadiazaborol[2,3-b][3,4-e]pyrano[1,3,2]-oxazaborine
Please cite this article in press as: Kotali, A.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.03.097

A. Kotali et al. / Tetrahedron xxx (2015) 1e5
5
(6g). Yellow needles (84%), mp 196e197 ꢁC; IR (KBr): 3440, 3093,
1721, 1640, 1548, 1498 cmꢀ1 1H NMR (CDCl3, 400 MHz):
1.95
14. Ma, X.-D.; Yang, S.-Q.; Gu, S.-X.; He, Q.-Q.; Chen, F.-E.; Clercq, E. D.; Balzarini, J.;
Pannecouque, C. ChemMedChem 2011, 6, 2225e2232.
15. Rahman, A. F. M.; Park, S.-E.; Kadi, A. A.; Kwon, Y. J. Med. Chem. 2014, 57,
.
d
(s, 3H), 2.35 (s, 3H), 2.88 (s, 1H), 6.16 (s, 1H), 7.16 (dd, J¼8.6, 3.8 Hz,
9139e9151.
2H), 7.59 (d, J¼4 Hz, 1H); 7.88 (d, J¼2.8 Hz, 1H) ppm; 13C NMR
16. Boyd, G. V. Synthesis and Reactions of Hydrazo, Azo and Azoxy Compounds; Patai’s
Chemistry of Functional Groups; John Wiley & Sons: Chichester, West Sussex,
UK, 2009.
17. Metwally, M. A.; Khalifa, M. E.; Koketsu, M. Am. J. Chem. 2012, 2, 38e51.
18. Smith, M. B. In March’s Advanced Organic Chemistry: Reactions, Mechanisms, and
Structure; John Wiley & Sons: Chichester, West Sussex, UK, 2013.
19. Joule, J. A.; Mills, K. In Heterocyclic Chemistry; John Wiley & Sons: Chichester,
West Sussex, UK, 2010.
(CDCl3, 100 MHz):
d 16.5, 20.7, 22.7, 99.9, 102.3, 128.1, 129.3, 132.2,
132.6, 160.6, 160.8, 165.0, 168.8, 170.3, 171.2 ppm; MS (ESIþ): m/z
383 (Mþ23), 301 (Mꢀ59). Anal. Calcd for C15H13BN2O6S: C, 50.02;
H, 3.64; N, 7.78. Found: C, 50.19; H, 3.63; N, 7.56.
20. Bellus, D.; Grimmett, M. R.; Hajos, G.; Mathey, F.; Neier, N.; Riedl, Z.; Schmid-
peter, A.; Stadlbauer, W.; Stanovnik, B. In Science of Synthesis, HoubeneWeyl
Methods of Molecular Transformations Five-Membered Hetarenes with Two
Nitrogen or Phosphorus; Georg Thieme: Stuttgart, 2014; Vol. 12.
21. (a) Katritzky, A. R.; Kotali, A. Tetrahedron Lett. 1990, 31, 6781e6784; (b) Kotali,
A.; Koulidis, A.; Harris, P. A.; Huey, M. W.; Ling, C. C. Org. Prep. Proced. Int. 1996,
28, 622e627; (c) Kotali, A.; Lafazanis, I. S.; Harris, P. A. Synthesis 2008, 836e840;
(d) Kotali, A.; Kotali, E.; Lafazanis, I. S.; Harris, P. A. Curr. Org. Chem. 2010, 7,
62e77; (e) Kotali, A.; Nasiopoulou, D. A.; Harris, P. A.; Helliwell, M.; Joule, J. A.
Tetrahedron 2012, 68, 761e766.
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Please cite this article in press as: Kotali, A.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.03.097