Pyrylium salts in the synthesis of 2-pyrazoline derivatives and earlier unknown substituted 3,3a,4,7-tetrahydropyrazolo[1,5-a]pyridin-7-ones

Article abstract of DOI:10.1007/s11172-007-0324-5

New 1,3,5-substituted 2-pyrazoline derivatives were synthesized from 2,6-diphenylpyrylium perchlorate and acylhydrazines. Method for the synthesis of earlier unknown 3,3a,4,7-tetrahydropyrazolo[1,5-a]pyridin-7-one derivatives from pyrylium salts and cyanoacetic acid hydrazide was proposed.

Full text of DOI:10.1007/s11172-007-0324-5

Russian Chemical Bulletin, International Edition, Vol. 56, No. 10, pp. 2085—2088, October, 2007
2085
Pyrylium salts in the synthesis of 2ꢀpyrazoline derivatives
and earlier unknown substituted
3,3a,4,7ꢀtetrahydropyrazolo[1,5ꢀa]pyridinꢀ7ꢀones
L. Yu. Ukhin
Scientific Research Institute of Physical and Organic Chemistry,
South Federal University,
194/2 prosp. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 243 4776. Еꢀmail: may@ipoc.rsu.ru
New 1,3,5ꢀsubstituted 2ꢀpyrazoline derivatives were synthesized from 2,6ꢀdiphenylpyrylium
perchlorate and acylhydrazines. Method for the synthesis of earlier unknown 3,3а,4,7ꢀtetraꢀ
hydropyrazolo[1,5ꢀa]pyridinꢀ7ꢀone derivatives from pyrylium salts and cyanoacetic acid hydrꢀ
azide was proposed.
Key words: pyrylium salts, acylhydrazines, 2ꢀpyrazoline derivatives, 3,3а,4,7ꢀtetraꢀ
hydropyrazolo[1,5ꢀa]pyridinꢀ7ꢀone derivatives.
Scheme 1
Pyrylium salts, known already for nearly 100 years, are
of permanent interest to chemists, which can be explained
by high reactivity and great diversity of transformations of
their carboxonium cations.1
The study of the reactions of pyrylium salts with pheꢀ
nylhydrazine2—5 showed that one of the main products
of the interaction of 2,4,6ꢀtriphenylpyrylium cation
with phenylhydrazine has cyclic 2ꢀpyrazoline structure.6
2ꢀPyrazoline derivatives were also obtained by the reacꢀ
tion of 2,4,6ꢀtriphenylpyrylium salt with ethoxycarboꢀ
nylhydrazine.7 It is also known8 that such pyrazolones
can undergo further cyclization to pyrazolo[2,3ꢀa]quinoꢀ
line derivatives. The simplicity of the synthesis and virtuꢀ
ally unlimited possibilities in variation of acid hydrazides
make them attractive starting compounds in the synthesis
of new potentially biologically active heterocycles from
pyrylium salts.
R =
(a),
(b), PhOCH2CO— (c),
We carried out the reaction of 2,6ꢀdiphenylpyrylium
perchlorate 1a with acid hydrazides 2a—c and оꢀcarboxyꢀ
phenylhydrazine 2d to isolate 2ꢀpyrazoline derivatives
3a—d in all the cases (Scheme 1).
(d)
It should be noted that pyrazoline 3c is also formed
with phenoxyacetic acid hydrazide 2c, which has the
methylene group, activated by the carbonyl function.
Quite different results were obtained in the reaction of
pyrylium salts with cyanoacetic acid hydrazide 2е, the
methylene group of which is activated by the two elecꢀ
tronꢀwithdrawing groups. In this case, the process did not
stop on the stage of the formation of pyrazolines, rather it
led to the earlier unknown tetrahydropyrazolo[1,5ꢀa]pyriꢀ
dinꢀ7ꢀone derivatives 4a—c. A proposed mechanism of
the reaction, which includes intramolecular condensaꢀ
tion of the methylene and carbonyl groups in the interꢀ
mediate pyrazolines 3e—f, is given in Scheme 2.
1H NMR spectra of compounds 4a—c (as well as of
pyrazolines 3a—d) have signals of the methylene and
methyne protons, characteristic of the ABꢀsystems. Mass
spectrometry data confirm their stoichiometry. The comꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2015—2017, October, 2007.
1066ꢀ5285/07/5610ꢀ2085 © 2007 Springer Science+Business Media, Inc.

2086
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
L. Yu. Ukhin
Scheme 2
UNITYꢀ300 spectrometer. Mass spectra were recorded on a
Finnigan MAT INCOS 50 chromatoꢀmass spectrometer with
direct inlet of a sample into the source of ions. The starting
pyrylium salts were synthesized according to the procedures
described earlier.9 Hydrazides 2a—е were obtained according to
the standard procedure10 from the corresponding acid esters and
hydrazine hydrate. Spectral characteristics of compounds obꢀ
tained are given in Table 1.
1ꢀ(2ꢀHydroxybenzoyl)ꢀ5ꢀphenacylꢀ3ꢀphenylꢀ2ꢀpyrazoline
(3a). A hot solution of salicylic hydrazide (2a) (0.46 g, 3 mmol)
was added to a boiling suspension of 2,6ꢀdiphenylpyrylium perꢀ
chlorate (1a) (1 g, 3 mmol) in МеOH (15 mL) and the reaction
mixture was refluxed for 5 min. The hot solution was placed into
a glass and cooled in an ice bath. The precipitate formed was
filtered off and recrystallized from EtOH (35 mL) to obtain
colorless crystalline substance with m.p. 166—167 °C. The yield
was 0.35 g (30%). Found (%): N, 7.37. C24H20N2O3. Calcuꢀ
lated (%): N, 7.28.
1ꢀ(2ꢀAminobenzoyl)ꢀ5ꢀphenacylꢀ3ꢀphenylꢀ2ꢀpyrazoline (3b).
A hot solution of anthranilic acid hydrazide (2b) (0.3 g, 2 mmol)
was added to a boiling suspension of salt 1a (0.66 g, 2 mmol) in
МеOH (10 mL). If the precipitate was not dissolved completely,
additional amount of hydrazide was used until complete dissoꢀ
lution of the pyrylium salt, then, the solution was refluxed for
20 min. The mixture was cooled, pyridine (1 mL) was added,
and the mixture was poured in iceꢀcold water, triturating with a
glass stick. The mixture was kept in an ice bath until complete
solidification, the precipitate was filtered off, washed with 50%
aqueous МеOH, and recrystallized from PriOH (80 mL). The
light yellow crystalline substance with m.p. 199—200 °C was
obtained. The yield was 0.26 g (33%). Found (%): N, 10.82.
R1 = Ph, R2 = H (a, e); R1 = But, R2 = H (b, f); R1 = R2 = Ph (c, g)
pounds are notable for the high stability. Thus, a proꢀ
longed reflux of 4a in HOAc or DMF does not cause
noticeable changes. Compound 4a dissolves in boiling
Ac2O and can crystallize from it upon cooling. At the
same time, it undergoes oxidation to 1Hꢀ2,5ꢀdiphenylꢀ6ꢀ
cyanopyrazolo[1,5ꢀa]pyridinꢀ7(1H )ꢀone 5 with such
atypical oxidant as NaN3 in boiling DMF (Scheme 3).
C24H21N3O2. Calculated (%): N, 10.96.
5ꢀPhenacylꢀ1ꢀphenoxyacetylꢀ3ꢀphenylꢀ2ꢀpyrazoline (3c).
Salt 1a (0.5 g, 1.5 mmol) was added to a solution of phenoxyacetic
acid hydrazide (2c) (0.35 g, 2 mmol) in DMF (5 mL), this was
kept for 10 min and heated to the boiling. After cooling, concenꢀ
trated NH4OH (3 mL) and H2O (10 mL) were added. The
precipitate with oil formed was cooled in an ice bath and trituꢀ
rated until complete solidification, filtered off, washed with H2O,
dried, and extracted with boiling isooctane (4×50 mL). The
precipitates, formed after cooling, were filtered off, combined
(the total yield was 0.4 g), and recrystallized from PriOH
(10 mL), cooling gradually (fast cooling leads to the formation
of a tar), to obtain colorless crystalline substance with m.p.
130 °C. The yield was 0.2 g (33%). Found (%): N, 7.27.
Scheme 3
C25H22N2O3. Calculated (%): N, 7.03.
1ꢀ(2ꢀCarboxyphenyl)ꢀ5ꢀphenacylꢀ3ꢀphenylꢀ2ꢀpyrazoline (3d).
A mixture of salt 1a (1.1 g, 3.3 mmol) and oꢀhydrazinobenzoic
acid (2d) (0.55 g, 3.6 mmol) was refluxed in МеOH (20 mL)
for 5—6 min, during which dissolution of the precipitate, formaꢀ
tion of new precipitate, and its dissolution took place. If the
new precipitate was not completely dissolved, additional amount
of acid was used. The reaction mixture was cooled, triturating
with a glass stick, kept in an ice bath for 1.5 h, the precipiꢀ
tate formed was filtered off, washed with cold МеOH, and
recrystallized from CH3CN (10 mL). Colorless crystalline
substance with m.p. 168—169 °C was obtained. The yield
was 0.28 g (22%). Found (%): N, 7.52. C24H20N2O3. Calcuꢀ
lated (%): N, 7.29.
Conditions: DMF, ∆, 5 h.
Experimental
IR spectra were recorded on a Specord IRꢀ75 spectrometer
in Nujol. 1H NMR spectra were recorded on a Varian
6ꢀCyanoꢀ2,5ꢀdiphenylꢀ3,3a,4,7ꢀtetrahydropyrazolo[1,5ꢀa]ꢀ
pyridinꢀ7ꢀone (4a). A hot solution of cyanoacetic acid hydrazide

Synthesis of pyrazolines and pyrazolinopyridones
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2087
Table 1. Spectral characteristics of compounds obtained
Comꢀ [M]+
pound
IR, ν/cm–1
(Nujol)
1H NMR
Solvent
δ (J/Hz)
3а
384
1680 (CO), 1627,
1595, 1580, 1567,
1554, 1487 (arom.)
DMSOꢀd6
3.10 (m, 1 Н, СН2); 3.41 (m, 1 Н, СН2); 3.64 (m, 1 Н, СН2);
3.96 (m, 1 Н, СН2); 5.18 (m, 1 Н, СН); 6.86 (m, 2 Н, СНarom);
7.20—7.80 (m, 9 Н, СНarom); 8.00 (d, 2 Н, СНarom, J = 7.5);
8.10 (d, 1 Н, СНarom, J = 7.3); 11.4 (s, 1 Н, ОН)
3b
383
3473, 3353 (NH2);
1667 (СО); 1627,
1607, 1574, 1554,
1487 (arom.)
DMSOꢀd6
3.05 (m, 1 Н, СН2); 3.40 (m, 1 Н, СН2); 3.61 (m, 1 Н, СН2);
3.95 (m, 1 Н, СН2); 5.12 (m, 1 Н, СН); 5.63 (br.s, 2 Н, NH2);
6.54 (br.t, 1 Н, СНarom); 6.71 (d, 1 Н, СНarom, J = 8.0);
7.10 (m, 1 Н, СНarom); 7.37 (m, 3 Н, СНarom); 7.45—7.70
(m, 6 Н, СНarom); 8.00 (br.d, 2 Н, СНarom
)
3c
3d
4а
398
384
1667, 1660, 1647 (СО);
1594, 1487 (arom.);
1214 (С—О—С)
CDCl3
DMSOꢀd6
CDCl3
3.11 (m, 2 Н, СН2); 3.66 (m, 1 Н, СН2); 4.22 (m, 1 Н, СН2);
5.14 (m, 3 Н, СН, СН2); 7.00 (m, 3 Н, СHarom);
7.30 (m, 3 Н, СНarom); 7.35—7.65 (m, 6 Н, СНarom);
7.74 (m, 2 Н, СНarom); 8.00 (m, 2 Н, СНarom
3.05 (m, 1 Н, СН2); 3.23 (m, 1 Н, СН2); 3.40 (m, 1 Н, СН2);
3.58 (m, 1 Н, СН2); 5.02 (m, 1 Н, СН); 6.92 (t, 1 Н, СНarom
)
1727, 1672 (СО);
1600, 1580, 1487,
1474 (arom.)
,
J = 7.3); 7.00—7.65 (m, 11 Н, СНarom); 7.88 (d, 2 Н, СНarom
,
J = 7.3); 12.44 (s, 1 Н, ОН)
3.10 (m, 2 Н, СН2); 3.38 (m, 1 Н, СН2); 3.62 (m, 1 Н, СН2);
4.44 (m, 1 Н, СН); 7.35—7.60 (m, 6 Н, СНarom);
313
273
2220 (CN); 1660 (СО);
1594, 1580, 1554, 1500,
1447, 1434 (arom.)
2220 (CN); 1674 (СО);
1594, 1580, 1480 (arom.)
2227 (CN); 1655 (СО);
1600, 1587, 1567, 1494,
1447, 1414 (arom.)
7.64 (br.d, 2 Н, СНarom); 7.86 (br.d, 2 Н, СНarom
)
4b
4с
CDCl3
CDCl3
1.24 (s, 9 Н, But); 1.40 (s, 9 Н, But); 2.45 (m, 1 Н, СН2);
2.63 (m, 1 Н, СН2); 3.11 (m, 1 Н, СН2); 3.95 (m, 1 Н, СН)
3.50 (d, 1 Н, СН2, J = 17.5); 3.65 (m, 2 Н, СН2);
3.89 (d, 1 Н, СН2, J = 17.5); 7.20—7.50 (m, 13 Н, СНarom);
7.80 (br.d, 2 Н, СНarom
)
5
311
2206 (CN); 1630 (СО);
1607, 1594, 1567,
DMSOꢀd6
6.55 (s, 1 Н, СНarom); 7.03 (s, 1 Н, СНarom);
7.30—7.60 (m, 8 Н, СНarom); 8.04 (m, 2 Н, СНarom
)
1554 (arom.)
(2е) (0.5 g, 5 mmol) in МеOH (10 mL) was added to a boiling
suspension of salt 1a (1 g, 3 mmol) in МеOH (10 mL), this was
refluxed for 1 min, cooled, and conc. NH4OH (20 mL) was
added. The precipitate formed was filtered off, washed few times
with H2O, EtOH, and recrystallized from CH3CN (50 mL).
Colorless crystalline substance with m.p. 291—292 °C was
obtained. The yield was 0.31 g (33%). Found (%): N, 13.48.
C20H15N3O. Calculated (%): N, 13.41.
6ꢀCyanoꢀ2,5ꢀdi(tertꢀbutyl)ꢀ3,3a,4,7ꢀtetrahydropyrazoꢀ
lo[1,5ꢀa]pyridinꢀ7ꢀone (4b). 2,6ꢀDi(tertꢀbutyl)pyrylium perchloꢀ
rate (0.585 g, 2 mmol) (1b) was dissolved in МеOH (10 mL)
under heating, a hot solution of hydrazide 2е (0.25 g, 2.5 mmol)
in МеOH (10 mL) was added, and this was refluxed for 5 min.
The solution was cooled, H2O (40 mL) and conc. NH4OH
(10 mL) were added, and this was kept for 6 h. The precipitate
formed was filtered off, washed with H2O, and dried to obtain
colorless needles with m.p. 255—256 °C (from PriOH). The
yield was 0.35 g (64%). Found (%): N, 15.69. C16H23N3O. Calꢀ
culated (%): N, 15.37.
(10 mL) and water were added to the filtrate to obtain a precipiꢀ
tate, which was filtered off and recrystallized from МеOH
(100 mL). Colorless crystalline substance with m.p. 283—284 °C
was obtained. The yield was 0.2 g (15%). Found (%): C, 79.93;
H, 5.17; N, 11.05. C26H19N3O. Calculated (%): C, 80.18;
H, 4.92; N, 10.79.
6ꢀCyanoꢀ2,5ꢀdiphenylpyrazolo[1,5ꢀa]pyridinꢀ7(1H )ꢀone (5).
A mixture of 4a (0.313 g, 1 mmol) and NaN3 (0.13 g, 2 mmol),
powdered in a mortar, was refluxed in DMF (10 mL) for 5 h
and cooled, HOAc (1 mL) and water were added to obtain a
precipitate, which was filtered off, washed with H2O, boiling
CH3CN, МеOH, and recrystallized from DMF. Colorless
crystalline substance with m.p. 323—325 °C was obtained.
In contrast to the starting compound, it was insoluble in
boiling CH3CN. Found (%): N, 13.50. C20H13N3O. Calcuꢀ
lated (%): N, 13.50.
References
6ꢀCyanoꢀ2,3a,5ꢀtriphenylꢀ3,3a,4,7ꢀtetrahydropyrazoꢀ
lo[1,5ꢀa]pyridinꢀ7ꢀone (4c). A mixture of 2,4,6ꢀtriphenylꢀ
pyrylium perchlorate (1c) (1.4 g, 3.4 mmol) and hydrazide 2е
(0.4 g, 4 mmol) was refluxed in МеOH (50 mL) until the preꢀ
cipitate was completely dissolved (~3.5 h), after cooling, the
precipitate formed was filtered off. Concentrated NH4OH
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L. Yu. Ukhin
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Received June 26, 2007