Synthesis of difluoroboron adamantyl-containing complexes and pyrazoles based thereon

Article abstract of DOI:10.1134/S1070428014110165

One-stage synthesis has been developed for the preparation of adamantyl-containing difluoroboron complexes of 1,3-dicarbonyl compounds from 1-(1-adamantyl)ethanone, boron trifluoride etherate, and carboxylic acids anhydrides. The reaction of the complexes with hydrazine hydrate and its derivatives afforded the corresponding adamantyl-containing pyrazoles.

Full text of DOI:10.1134/S1070428014110165

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 11, pp. 1636–1638. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © S.A. Kon’kov, K.S. Krylov, K.M. Bormasheva, I.K. Moiseev, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50,
No. 11, pp. 1649–1651.
Synthesis of Difluoroboron Adamantyl-Containing Complexes
and Pyrazoles Based Thereon
S. A. Kon’kova, K. S. Krylovb, K. M. Bormashevaa, and I. K. Moiseeva
a Samara State Technical University, ul. Molodogvardeiskaya 244, Samara, 443100 Russia
e-mail: ikmoiseev@mail.ru
b Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received March 14, 2013
Abstract—One-stage synthesis has been developed for the preparation of adamantyl-сontaining difluoroboron
complexes of 1,3-dicarbonyl compounds from 1-(1-adamantyl)ethanone, boron trifluoride etherate, and carbo-
xylic acids anhydrides. The reaction of the complexes with hydrazine hydrate and its derivatives afforded the
corresponding adamantyl-containing pyrazoles.
DOI: 10.1134/S1070428014110165
Chemistry of five-membered heterocycles attracts
the attention of researchers because of their practical
importance and biologic activity. We recently des-
cribed the synthesis and antiviral activity of ada-
mantyl-containing heterocycles obtained by the reac-
tion of 1,3-diketones with hydrazine and its derivatives
[1, 2].
Compounds Ia and Ib are characterized by a good
thermal stability, but they are decomposed under the
action of Na2CO3 in alcohol giving the corresponding
diketones IIa and IIb.
An interesting feature of difluoroboron complexes
Ia and Ib is their readily reacting with various
bifunctional compounds. Under the treatment with
hydrazine and its versatile substituted derivatives
complexes Ia and Ib decompose and apparently form
in situ 1,3-diketones that react with appropriate bi-
nucleophiles to provide pyrazoles IIIа, IIIb–VIIIа,
and VIIIb (Scheme 2). The yields of pyrazoles at the
synthesis from the difluoroboron complexes Ia and Ib
and diketones IIa and IIb are practically the same. The
structure of products of the reaction between
unsymmetrical adamantyl-containing 1,3-diketones
with substituted hydrazines was proved by NMR
A promising direction in the adamantane chemistry
is the synthesis and study of the properties of difluoro-
boron complexes. Difluoroboron complexes having a
betaine structure [3] are commonly prepared from 1,3-
dicarbonyl compounds by treating the latter with boron
trifluoride etherate or gaseous boron trifluoride.
We developed a simple and convenient method of
the one-stage synthesis of difluoroboron complexes
consisting in the reaction of 1-(1-adamantyl)ethanone
with acid anhydrides in the presence of boron tri-
fluoride etherate (Scheme 1).
1
spectroscopy involving 2D heteronuclear methods H,
1
13C and H, 15N HMBC by examples of the reactions
Scheme 1.
R
O
R
R
BF3·Et2O
Na2CO3, Δ
i-PrOH
O+
O
Me
+
O
_
Δ
R
B
O
O
F
O
O
F
Ia, Ib
IIa, IIb
R = Me (а), Et (b).
1636

SYNTHESIS OF DIFLUOROBORON ADAMANTYL-CONTAINING COMPLEXES
1637
Scheme 2.
63.99; Н 7.67. С15Н21BF2O2. Calculated, %: С 63.83;
Н 7.45.
R
1-(1-Adamantyl)butane-1,3-dione (IIа). To a so-
lution of 2.2 g (8.21 mmol) of compound Ia in 20 mL
of 2-propanol and 2 mL of water was added 4.35 g
(41.05 mmol) of Na2CO3, and the mixture was boiled
for 5 h. On cooling the solution was acidified till рН 7
and extracted with chloroform. The organic layer was
dried with Na2SO4, the solvent was distilled off, the
residue was recrystallized from 2-propanol. Yield 1.2 g
(73%), colorless crystals, mp 52–53°С (53–56°С [5]).
R'NHNH2, Δ
EtOH_i-PrOH
R'NHNH2, Δ
EtOH_i-PrOH
Ia, Ib
N
IIa, IIb
N
R'
IIIa, IIIb–VIIIa, VIIIb
R = Me (a), Et (b); R' = Н (III), Me (IV), Ph (V),
4-NO2C6H4 (VI), 2,4-(NO2)2C6H4 (VII), 3,5-Cl2Py-2 (VIII).
of diketone IIa with phenylhydrazine and hydroxyl-
amine [4].
1-(1-Adamantyl)pentane-1,3-dione (IIb) was
obtained similarly from 3 g (10.64 mmol) of
compound Ib, 35 mL of 2-propanol, 3 mL of water,
5.62 g (53.02 mmol) of Na2CO3. Yield 2.3 g (92%),
colorless crystals (at room temperature viscous oily
substance), mp 32°С (2-propanol, 40°С [1]).
EXPERIMENTAL
IR spectra of compounds synthesized were recor-
ded on a spectrophotometer Shimadzu FTIR-8400S
1
from pellets with KBr. Н NMR spectra were regis-
5-(1-Adamantyl)-3-methyl-1Н-pyrazole (IIIа).
To a solution of 1 g (3.73 mmol) of compound Ia in
10 mL of ethanol was added 0.55 g (7.4 mmol) of
hydrazine hydrate, the mixture was boiled for 5 h and
cooled. The separated precipitate was filtered off,
recrystallized from ethanol. Yield 0.75 g (93%),
colorless crystals, mp 193–195°С (193–195.5°С [1]).
tered on spectrometers Bruker AM-400 (400 MHz),
internal reference TMS, solvent DMSO-d6 (IIIа, IIIb,
Vа, Vb, and VIIIа), and Jeol JNM-ECS400 (400 MHz),
internal reference TMS, solvent CDCl3 (Iа, Ib, IIа,
IIb, IVа, IVb–VIIа, VIIb, and VIIIb). Elemental
analysis was carried out on an analyzer EuroVector
EA-3000. The purity of compounds was checked by
TLC (on Silufol and Sorbfil plates, eluent CCl4−acetone,
1 : 1, 5 : 1, and 10 : 1.)
Compounds IIIа, IIIb–VIIIа, and VIIIb were ana-
logously prepared.
5-(1-Adamantyl)-3-ethyl-1Н-pyrazole (IIIb) was
obtained from 1 g (3.55 mmol) of compound Ib and
0.46 g (7.1 mmol) of hydrazine hydrate. Yield 0.72 g
(88%), colorless crystals, mp 170–173°С (ethanol,
174–178°С [1]).
4-(1-Adamantyl)-2,2-difluoro-6-methyl-1,3,2-di-
oxaborium-2-uide (Ia). To a mixture of 20 g (112 mmol)
of 1-(1-adamantyl)ethanone with 22.84 g (224 mmol)
of acetic anhydride was added 41.84 mL (330 mmol)
of boron trifluoride etherate. The reaction mixture was
boiled for 5 h and cooled. The separated precipitate
was filtered off, washed with water, and dried. Yield
22.88 g (76%), colorless crystals, mp 162–163°С (i-
PrOH). IR spectrum, ν, cm–1: 2912, 2852 (C−HAd),
5-(1-Adamantyl)-1,3-dimethyl-1Н-pyrazole
(IVа) was obtained from 1 g (3.73 mmol) of
compound Ia and 0.34 g (7.46 mmol) of methyl-
hydrazine. Yield 0.75 g (87%), light yellow crystals,
mp 110–112°С. IR spectrum, ν, cm–1: 2904, 2850
(C−HAd), 1539, 1446 (C=C, C=N). 1Н NMR spectrum,
δ, ppm: 1.70–2.10 m (15Н, Аd), 2.20 s (3Н, СН3), 3.90
s (3Н, СН3N), 5.75 s (1Н, СН). Found, %: С 78.50; Н
9.51; N 12.18. С15Н22N2. Calculated, %: С 78.26; Н
9.57; N 12.17.
1
1539 (C=C). Н NMR spectrum, δ, ppm: 1.69–2.10 m
(15Н, Аd), 2.31 s (3Н, СН3), 6.01 s (1H, CH=C).
Found, %: С 62.83; Н 7.23. С14Н19BF2O2. Calculated,
%: С 62.69; Н 7.09.
4-(1-Adamantyl)-2,2-difluoro-6-ethyl-1,3,2-di-
oxaborinin-1-ium-2-uide (Ib) was obtained similarly
from 21.50 g (224 mmol) of propionic anhydride.
Yield 22.18 g (70%), colorless crystals, mp 114–115°С
(i-PrOH). IR spectrum, ν, cm–1: 2912, 2852 (C−HAd),
1550 (C=C). 1Н NMR spectrum, δ, ppm: 1.10 t (3Н,
СН3, J 12 Hz), 1.23–2.36 m (15Н, Аd), 2.76 q (2Н,
СН2, J 12 Hz), 5.51 s (1Н, СН=С). Found, %: С
5-(1-Adamantyl)-3-ethyl-1-methyl-1Н-pyrazole
(IVb) was obtained from 1 g (3.55 mmol) of com-
pound Ib and 0.35 g (7.1 mmol) of methylhydrazine.
Yield 0.73 g (84%), light yellow crystals, mp 62–64°С.
IR spectrum, ν, cm–1: 2904, 2846 (C−HAd), 1535, 1450
1
(C=C, C=N). Н NMR spectrum, δ, ppm: 1.20 t (3Н,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

KON’KOV et al.
1638
СН3, J 12 Hz), 1.91–2.06 m (15Н, Аd), 2.53 q (2Н,
СН2, J 12 Hz), 3.88 s (3Н, СН3N), 5.79 s (1Н, СН).
Found, %: С 78.80; Н 9.90; N 11.58. С16Н24N2.
Calculated, %: С 78.69; Н 9.84; N 11.48.
5-(1-Adamantyl)-1-(2,4-dinitrophenyl)-3-ethyl-1Н-
pyrazole (VIIb) was obtained from 1 g (3.55 mmol) of
compound Ib and 0.70 g (3.55 mmol) of (2,4-dinit-
rophenyl)hydrazine. Yield 1.24 g (89%), orange crys-
tals, mp 140–144°С. IR spectrum, ν, cm–1: 2904, 2846
(C−HAd), 1600, 1543, 1450 (C=C/C=N), 799 (C−HAr).
1Н NMR spectrum, δ, ppm: 1.19 t (3Н, СН3, J 12 Hz),
1.50–2.00 m (15Н, Аd), 2.56 q (2Н, СН2, J 12 Hz), 6.10
s (1Н, СН), 7.80 d (1НAr, Н6', J 8 Hz), 8.51 q (1НAr,
Н5', J 16 Hz), 8.88 d (1НAr, Н3', J 8 Hz). Found, %: С
63.67; Н 6.09; N 14.23. С21Н24N4O4. Calculated, %: С
63.64; Н 6.06; N 14.14.
5-(1-Adamantyl)-3-methyl-1-phenyl-1Н-pyrazo-
le (Vа) was obtained from 1 g (3.73 mmol) of com-
pound Ia and 0.41 g (3.7 mmol) of phenylhydrazine.
Yield 0.97 g (90%), yellow crystals, mp 68–70°С
(ethanol), 73–76°С [1]).
5-(1-Adamantyl)-3-ethyl-1-phenyl-1Н-pyrazole
(Vb) was obtained from 1 g (3.55 mmol) of compound
Ib and 0.38 g (3.55 mmol) of phenylhydrazine. Yield
0.95 g (87%), yellow crystals, mp 112–114°С (ethanol,
113–115°С [1]).
2-[5-(1-Adamantyl)-3-methyl-1Н-pyrazol-1-yl]-
3,5-dichloropyridine (VIIIа) was obtained from 1 g
(3.73 mmol) of compound Ia and 0.66 g (3.73 mmol)
of 2-hydrazinyl-3,5-dichloropyridine. Yield 1.28 g (95%),
colorless crystals, mp 124–126°С. IR spectrum, ν, cm–1:
3058 (C−HPy), 2893, 2850 (C−HAd), 1542, 1454 (C=C,
5-(1-Adamantyl)-3-methyl-1-(4-nitrophenyl)-1Н-
pyrazole (VIа) was obtained from 1 g (3.73 mmol) of
compound Ia and 0.57 g (3.7 mmol) of (4-nitro-
phenyl)hydrazine. Yield 1.10 g (88%), yellow crys-
tals, mp 160–162°С. IR spectrum, ν, cm–1: 2908, 2850
(C−HAd), 1596, 1524, 1497, 1446 (C=C/C=N), 840,
802 (C−HAr). 1Н NMR spectrum, δ, ppm: 1.55–2.16 m
(15Н, Аd), 2.26 s (3Н, СН3), 6.01 s (1Н, СН), 7.55 d
(2НAr, H2',6', J 8 Hz), 8.30 d (2НAr, H3',5', J 8 Hz).
Found, %: С 71.30; Н 6.91; N 12.41. С20Н23N3O2.
Calculated, %: С 71.23; Н 6.82; N 12.46.
1
C=N), 786, 759 (C−HAr). Н NMR spectrum, δ, ppm:
1.37–2.01 m (15Н, Аd), 2.12 s (3Н, СН3), 6.01 s (1Н,
СН), 8.49 s (1Н, Н4 Py), 8.63 s (1Н, Н6 Py). Found, %:
С 63.08; Н 5.88; N 11.71. С19Н21Cl2N3. Calculated, %:
С 62.98; Н 5.80; N 11.60.
2-[5-(1-Adamantyl)-3-ethyl-1Н-pyrazol-1-yl]-
3,5-dichloropyridine (VIIIb) was obtained from 1 g
(3.55 mmol) of compound Ib and 0.63 g (3.55 mmol)
of 2-hydrazinyl-3,5-dichloropyridine. Yield 1.21 g
(91%), colorless crystals, mp 108°С. IR spectrum, ν,
cm–1: 3051 (C−HPy), 2855, 2847 (C−HAd), 1539, 1423
5-(1-Adamantyl)-3-ethyl-1-(4-nitrophenyl)-1Н-
pyrazole (VIb) was obtained from 1 g (3.55 mmol) of
compound Ib and 0.54 g (3.55 mmol) of (4-nitrophe-
nyl)hydrazine. Yield 1.05 g (85%), orange crystals, mp
156–158°С. IR spectrum, ν, cm–1: 2904, 2850
(C−HAd), 1596, 1523, 1496, 1450 (C=C/C=N), 841, 802
(C−HAr). 1Н NMR spectrum, δ, ppm: 1.20 t (3Н, СН3, J
12 Hz), 1.52–2.15 m (15Н, Аd), 2.62 q (2Н, СН2, J
20 Hz), 6.04 s (1Н, СН), 7.55 d (2НAr, H2',6', J 8 Hz),
8.29 d (2НAr, H3',5', J 8 Hz). Found, %: С 71.83; Н 7.34;
N 12.01. С21Н25N3O2. Calculated, %: С 71.79; Н 7.12;
N 11.97.
1
(C=C/C=N), 798, 763 (C−HAr). Н NMR spectrum, δ,
ppm: 1.27 t (3Н, СН3), 1.59–1.97 m (15Н, Аd), 2.67 q
(2Н, СН2, J 12 Hz), 6.07 s (1Н, СН), 7.93 s (1Н, Н4 Py),
8.50 s (1Н, Н6 Py). Found, %: С 63.96; Н 6.23; N 11.22.
С20Н23Cl2N3. Calculated, %: С 63.83; Н 6.12; N 11.17.
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1Н-pyrazole (VIIа) was obtained from 1 g (3.73 mmol)
of compound Ia and 0.74 g (3.73 mmol) of (2,4-dinit-
rophenyl)hydrazine. Yield 1.30 g (91%), yellow crys-
tals, mp 202–204°С. IR spectrum, ν, cm–1: 2908, 2850
(C−HAd), 1600, 1542, 1450 (C=C/C=N), 787 (C−HAr).
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2.20 s (3Н, СН3), 6.10 s (1Н, СН), 7.86 d (1НAr, Н6', J
8 Hz), 8.52 q (1НAr, Н5', J 11.5 Hz), 8.90 d (1НAr,
Н3', J 8 Hz). Found, %: С 62.90; Н 5.87; N 14.67.
С20Н22N4O4. Calculated, %: С 62.83; Н 5.76; N 14.66.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014