Reactions of 3-ethoxymethylidenepentane-2,4-dione and ethyl 2-ethoxymethylidene-3-oxobutanoate with benzohydrazide

Full text of DOI:10.1134/S1070428008040271

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 4, pp. 621–623. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © S.I. Yakimovich, I.V. Zerova, V.V. Pakal’nis, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 4, pp. 625–627.
SHORT
COMMUNICATIONS
Reactions of 3-Ethoxymethylidenepentane-2,4-dione and Ethyl
2-Ethoxymethylidene-3-oxobutanoate with Benzohydrazide
S. I. Yakimovich, I. V. Zerova, and V. V. Pakal’nis
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: viktoriapakalnis@mail.ru
Received November 7, 2007
DOI: 10.1134/S1070428008040271
It is known that alkoxymethylidene derivatives of
1,3-dicarbonyl compounds react with acylhydrazines at
elevated temperature to give the corresponding 3,4-di-
substituted N-acylpyrazoles [1, 2]. Using the reaction
of 3-ethoxymethylidenepentane-2,4-dione (Ia) with
benzohydrazide as an example, we have demonstrated
that the primary condensation product, conjugated ene-
hydrazine IIa, can be isolated and characterized when
the reaction is performed in methanol at room tempera-
ture in the absence of a catalyst. Enehydrazine IIa in
methanol is gradually converted into 4,5-disubstituted
N-benzoylpyrazole IIIa which can be isolated by
careful removal of the solvent under reduced pressure.
Most probably, compound IIIa is formed through
intermediate hydrazone A (it cannot be detected) and
5-hydroxy-4,5-dihydro-1H-pyrazole structure B [3].
same process also occurs at room temperature but at
a very low rate. Presumably, the driving force of this
isomerization is considerably weaker steric interac-
tions between the substituents in the pyrazole ring of
IVa as compared to IIIa. Pyrazole IVa was also
formed when enehydrazine IIa was heated in boiling
toluene.
Analogous results were obtained in the reaction of
ethyl 2-ethoxymethylidene-3-oxobutanoate (Ib) with
benzohydrazide. Enehydrazine IIb in solution exists as
a mixture of Z and and E isomers; on keeping in
methanol, compound IIb is completely converted into
pyrazole IIIb. The reaction is chemoselective: the ester
group is not involved in the cyclization. Heating of
pyrazole IIIb in boiling toluene gives 3,4-disubstituted
N-benzoylpyrazole IVb.
N-Benzoylpyrazole IIIa in boiling toluene under-
goes fairly fast and irreversible transformation into
4-acetyl-1-benzoyl-3-methyl-1H-pyrazole (IVa). The
Thus reactions of alkoxymethylidene derivatives of
1,3-dicarbonyl compounds with acylhydrazines can be
used to synthesize not only previously known con-
R
O
O
O
O
MeOH, 20°C
+
R
Me
OEt
Ia, Ib
NH2
Ph
N
HN NH
O
H
Ph
Me
O
IIa, IIb
O
O
O
R
H
Me
R
R
R
O
O
PhMe, Δ
HO
Me
N
N
N
HN
O
N
–H2O
Me
N
N
N
Ph
Me
O
Ph
O
Ph
O
Ph
A
B
IIIa, IIIb
IVa, IVb
R = Me (a), EtO (b).
621

YAKIMOVICH et al.
622
jugated enehydrazines and 3,4-disubstituted N-acyl-
pyrazoles but also isomeric 4,5-disubstituted N-acyl-
pyrazoles.
removed under reduced pressure, and the precipitate
was filtered off and washed with cold methanol. Yield
0.267 g (78%), mp 85–86°C. H NMR spectrum
1
(CDCl3), δ, ppm: 2.53 s (3H, COCH3), 2.98 s (3H,
5-CH3), 7.52 t (2H, m-H, J = 7.3 Hz), 7.65 t (1H, p-H,
J = 7.3 Hz), 7.95 d (2H, o-H, J = 7.3 Hz), 7.99 s (1H,
3-H). 13C NMR spectrum (CDCl3), δC, ppm: 13.48
(5-CH3); 29.88 (COCH3); 122.98 (C4); 128.58, 131.82,
132.20, 133.91 (Carom); 143.22 (C5); 148.59 (C3);
169.07 (PhCO); 194.03 (CH3CO). Found, %: C 68.36;
H 5.21; N 12.17. C13H12N2O2. Calculated, %: C 68.42;
H 5.26; N 12.28.
Initial 3-ethoxymethylidenepentane-2,4-dione (Ia)
and ethyl 2-ethoxymethylidene-3-oxobutanoate (Ib)
were synthesized according to the procedures reported
in [4, 5].
N′-(2-Acetyl-3-oxobut-1-en-1-yl)benzohydrazide
(IIa). A solution of 0.340 g (2.5 mmol) of benzohydra-
zide in 5 ml of anhydrous methanol was added drop-
wise under stirring to a solution of 0.390 g (2.5 mmol)
of compound Ia in 4 ml of anhydrous methanol on
cooling to 3–5°C. The precipitate was filtered off and
washed with cold anhydrous methanol. Yield 0.603 g
(98%), mp 169–170°C. 1H NMR spectrum (DMSO-d6),
δ, ppm: 2.23 s (3H, CH3), 2.37 s (3H, CH3), 7.54 t (2H,
m-H, J = 7.3 Hz), 7.62 t (1H, p-H, J = 7.3 Hz), 7.90 d
(2H, o-H, J = 7.3 Hz), 8.17 d (1H, HC=C, J =
10.2 Hz), 11.69 br.s (1H, NH), 12.28 br.d (1H, NH,
J = 10.9 Hz). Found, %: C 63.35; H 5.68; N 11.30.
C13H14N2O3. Calculated, %: C 63.41; H 5.69; N 11.38.
Ethyl 1-benzoyl-5-methyl-1H-pyrazole-4-carbox-
ylate (IIIb) was synthesized in a similar way from
0.414 g (1.5 mol) of compound IIb. Yield 0.317 g
1
(82%), mp 78–79°C. H NMR spectrum (CDCl3), δ,
ppm: 1.40 t (3H, CH2CH3, J = 7.3 Hz), 2.97 s (3H,
5-CH3), 4.37 q (2H, OCH2, J = 7.3 Hz), 7.51 t (2H,
m-H, J = 7.3 Hz), 7.64 t (1H, p-H, J = 7.3 Hz), 7.95 d
(2H, o-H, J = 7.3 Hz), 8.01 s (1H, 3-H). 13C NMR
spectrum (CDCl3), δC, ppm: 13.41 (5-CH3); 14.22
(CH2CH3); 61.05 (OCH2); 116.23 (C4); 128.62, 131.02,
132.17, 133.80 (Carom); 142.17 (C5); 148.89 (C3);
163.71 (4-CO); 164.97 (PhCO). Found, %: C 65.06;
H 5.40; N 10.79. C14H14N2O3. Calculated, %: C 65.12;
H 5.43; N 10.85.
Ethyl 2-acetyl-3-(2-benzoylhydrazino)prop-2-
enoate (IIb) was synthesized in a similar way from
0.558 g (3 mmol) of compound IIb and 0.408 g
(3 mmol) of benzohydrazide. Yield 0.695 g (84%),
mp 109–110°C. 1H NMR spectrum, δ, ppm: in CDCl3:
E isomer (82%): 1.28 t (3H, CH2CH3, J = 7.3 Hz),
2.46 s (3H, COCH3), 4.17 q (2H, OCH2, J = 7.3 Hz),
7.45–7.89 m (5H, Harom), 8.12 d (1H, HC=C, J =
10.9 Hz), 9.39 br.s (1H, NH), 12.02 d (1H, NH, J =
10.9 Hz); Z isomer (18%): 1.38 t (3H, CH2CH3, J =
7.3 Hz), 2.43 s (3H, COCH3), 4.31 q (2H, OCH2, J =
7.3 Hz), 7.45–7.93 m (5H, Harom), 8.53 d (1H, HC=C,
J = 12.4 Hz), 10.83 br.s (1H, NH), 11.12 d (1H, NH,
J = 12.4 Hz); in DMSO-d6: E isomer (94%): 1.24 t
(3H, CH2CH3, J = 7.3 Hz), 2.40 s (3H, COCH3),
4.13 q (2H, OCH2, J = 7.3 Hz), 7.51–7.90 m (5H,
4-Acetyl-1-benzoyl-3-methyl-1H-pyrazole (IVa).
A solution of 0.342 g (1.5 mmol) of pyrazole IIIa in
8 ml of anhydrous toluene was heated for 8 h under
reflux. The solvent was distilled off under reduced
pressure, and the residue was recrystallized from
petroleum ether. Yield 0.291 g (85%), mp 110–111°C.
1H NMR spectrum (CDCl3), δC, ppm: 2.54 s (3H,
CH3), 2.55 s (3H, CH3), 7.54 t (2H, m-H, J = 7.3 Hz),
7.66 t (1H, p-H, J = 7.3 Hz), 8.17 d (2H, o-H, J =
7.3 Hz), 8.84 s (1H, 5-H). 13C NMR spectrum (CDCl3),
δC, ppm: 14.85 (3-CH3); 28.95 (COCH3); 123.73 (C4);
128.67, 130.94, 132.21, 134.03 (Carom); 135.19 (C5);
154.79 (C3); 166.38 (PhCO); 193.37 (CH3CO). Found,
%: C 68.40; H 5.26; N 12.23. C13H12N2O2. Calculated,
%: C 68.42; H 5.26; N 12.28.
H
arom), 8.16 d (1H, HC=C, J = 10.9 Hz), 11.77 br.s
(1H, NH), 12.42 d (1H, NH, J = 10.9 Hz); Z isomer
(6%): 1.29 t (3H, CH2CH3, J = 7.3 Hz), 2.34 s (3H,
COCH3), 4.24 q (2H, OCH2, J = 7.3 Hz), 7.45–7.90 m
(5H, Harom), 8.05 d (1H, HC=C, J = 12.4 Hz),
11.77 br.s (1H, NH), 10.50 d (1H, NH, J = 12.4 Hz).
Found, %: C 60.80; H 5.69; N 10.11. C14H16N2O4. Cal-
culated, %: C 60.87; H 5.80; N 10.14.
Ethyl 1-benzoyl-3-methyl-1H-pyrazole-4-carbox-
ylate (IVb) was synthesized in a similar way from
0.387 g (1.5 mmol) of pyrazole IIIb; the product was
recrystallized from hexane. Yield 0.310 g (80%),
1
mp 36–37°C. H NMR spectrum (CDCl3), δ, ppm:
4-Acetyl-1-benzoyl-5-methyl-1H-pyrazole (IIIa).
A mixture of 0.369 g (1.5 mmol) of hydrazide IIa and
6 ml of anhydrous methanol was kept at room tem-
perature until complete dissolution. The solvent was
1.39 t (3H, CH2CH3, J = 7.3 Hz), 2.56 s (3H, 3-CH3),
4.35 q (2H, OCH2, J = 7.3 Hz), 7.53 t (2H, m-H, J =
7.3 Hz), 7.65 t (1H, p-H, J = 7.3 Hz), 8.16 d (2H, o-H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008

REACTIONS OF 3-ETHOXYMETHYLIDENEPENTANE-2,4-DIONE
J = 7.3 Hz). 8.82 s (1H, 5-H). 13C NMR spectrum
623
REFERENCES
(CDCl3), δC, ppm: 14.27 (CH2CH3); 14.68 (3-CH3);
61.00 (OCH2); 116.65 (C4); 128.61, 131.06, 132.14,
133.85 (Carom); 135.51 (C5); 154.93 (C3); 163.23
(4-CO); 166.07 (PhCO). Found, %: C 65.08; H 5.38;
N 10.79. C14H14N2O3. Calculated, %: C 65.12; H 5.43;
N 10.85.
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1
The H and 13C NMR spectra were measured on
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008