Substituted butanolides and butenolides: XVI. Oxidative and hydrolytic transformations of butanolide fused to dihydropyrazole ring

Article abstract of DOI:10.1023/A:1020818116077

Reactions of 3a,4,6,6a-tetrahydro-3H-furo[3,4-c]pyrazol-6-one with chlorine and bromine give the corresponding 2,6-dihydro-4H-furo[3,4-c]pyrazol-6-one hydrohalides. Hydrolysis of 3a,4,6,6a-tetrahydro-3H-furo[3,4-c]pyrazol-6-one is accompanied by oxidation

Full text of DOI:10.1023/A:1020818116077

Russian Journal of Organic Chemistry, Vol. 38, No. 7, 2002, pp. 1042 1045. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 7, 2002,
pp. 1085 1088.
Original Russian Text Copyright
2002 by Tyukhteneva, Badovskaya.
Substituted Butanolides and Butenolides: XVI.* Oxidative
and Hydrolytic Transformations of Butanolide Fused
to Dihydropyrazole Ring
Z. I. Tyukhteneva and L. A. Badovskaya
Kuban State University of Technology, ul. Moskovskaya 2, Krasnodar, 350072 Russia
e-mail: k-obh@kubstu.ru
Received September 7, 2001
Abstract Reactions of 3a,4,6,6a-tetrahydro-3H-furo[3,4-c]pyrazol-6-one with chlorine and bromine give the
corresponding 2,6-dihydro-4H-furo[3,4-c]pyrazol-6-one hydrohalides. Hydrolysis of 3a,4,6,6a-tetrahydro-3H-
furo[3,4-c]pyrazol-6-one is accompanied by oxidation of the dihydropyrazole ring to pyrazole and opening
of the lactone ring.
We previously described the synthesis of 3a,4,6,6a-
tetrahydro-3H-furo[3,4-c]pyrazol-6-one (I) and its
isomerization to 2,3a,4,6-tetrahydro-3H-furo[3,4-c]-
pyrazol-6-one (II) in the presence of acids and bases
[2]. It was convenient to monitor the isomerization
process by UV spectroscopy. Compound I shows
in the electron spectrum an absorption maximum at
We have effected oxidation of 3a,4,6,6a-tetrahydro-
3H-furo[3,4-c]pyrazol-6-one (I) with chlorine in
chloroform to obtain 2,6-dihydro-4H-furo[3,4-c]pyra-
zol-6-one (III). The reaction of I with bromine gave
hydrobromide IV (Scheme 1). The transformation of
dihydropyrazole ring into pyrazole was also observed
when dry hydrogen chloride was passed through
a boiling solution of compound I in alcohol. The
product was isolated as hydrochloride V. The oxida-
tion with chlorine and bromine is fast; nevertheless, in
the reaction with hydrogen chloride we succeeded in
detecting intermediate dihydropyrazole derivative II
*
320 nm due to n, transition in the azo group,
which is typical of 4,5-dihydro-3H-pyrazoles. The
absorption maximum of compound II is located at
276 nm, which is typical of compounds containing
a CH N bond conjugated with ester moiety.
Scheme 1.
____________
*
For communication XV, see [1].
1070-4280/02/3807-1042$27.00 2002 MAIK Nauka/Interperiodica

SUBSTITUTED BUTANOLIDES AND BUTENOLIDES: XVI.
1043
Table 1. Yields, melting points, and elemental analyses of compounds III VI
Found, %
Calculated, %
Comp. Yield,
mp,
C
Formula
Rf
no.
%
C
H
N
Hlg
C
H
N
Hlg
III
IV
V
78
83
71
48
190
47.92 3.40 22.38
C5H4N2O2
48.39 3.23 22.58
0.18
0.57
185a
142
225
29.61 2.40 13.25 39.00
37.59 3.18 17.32 21.86
42.58 4.51 19.42
C5H5BrN2O2
C5H5ClN2O2
C5H6N2O3
29.27 2.44 13.66 39.02
37.38 3.12 17.46 22.12
42.25 4.26 19.72
VI
a
With decomposition.
Table 2. UV and IR spectra of compounds III VI
1
IR spectrum, , cm
C N
Comp. UV spectrum (H2O),
no.
max, nm (log )
C O
N H
CHarom
NH
III
IV
223 (4.07)
223 (3.49)
1710
1795
3135, 3240
3440
1625
1620
3040, 945, 790
3035, 3005, 935,
840
3040, 3015, 940,
845
2460, 2780
2450, 2720
V
225 (3.38)
216 (3.21)
1800
1710
3370
3155
1630
1660
VI
3030, 960, 800
by spectrophotometry. Presumably, the oxidation with
halogens includes the same transformation sequence.
Oxidation of dihydropyrazoles has been extensively
studied [3]. Most frequently, the main oxidation
products are pyrazoles which are thermodynamically
stable systems.
The assumed structures of compounds III V are
confirmed by the data of elemental analysis (Table 1)
and UV and IR spectroscopy (Table 2). Their UV
spectra contain an absorption maximum at 223 nm.
According to [4], the K band of unsubstituted pyrazole
is located at 211 nm. The red shift of the absorption
maximum of compounds III V results from conjuga-
tion with the lactone carbonyl group. The latter acts
as auxochrome, leading to characteristic spectral
changes. The absorption maxima in the UV spectra of
salts IV and V also appear at 223 nm, presumably
due to their complete hydrolysis in aqueous medium.
carbonyl absorption bands in the spectra of pyrazole
III and its salts IV and V are considerably different.
The C O band of III suffers a strong low-frequency
1
shift (1710 cm ) relative to the corresponding band
1
of I (1780 cm ), which may be due to conjugation
of the lactone carbonyl group with heteroaromatic
pyrazole ring: The planar C C(O) O C moiety
in the butanolide ring [5] is coplanar to the pyrazole
ring plane, giving rise to a relatively long conjugation
chain. The pyrazole ring in salts IV and V has a posi-
tive charge; as a result, conjugation with the lactone
carbonyl group weakens, and stretching vibration
1
band of the latter is observed at 1795 and 1800 cm ,
respectively. In addition, the IR spectra of salts IV
and V contain a set of strong broadened bands in the
1
region 2450 2780 cm , which arise from vibrations
+
of the HN fragment [6].
To estimate the stability of dihydropyrazole ring
Compound III shows in the IR spectrum absorp-
fused to butanolide ring, compound I was subjected
tion bands belonging to the pyrazole ring: broadened to hydrolysis in acid and alkaline medium (Scheme 2).
1
bands in the region 3200 3400 cm correspond to
stretching vibrations of associated N H bonds, a band
The transformation of the dihydropyrazole ring was
monitored by spectrophotometry, and accumulation
of acids was monitored by acid base titration. The
hydrolysis of 3a,4,6,6a-tetrahydro-3H-furo[3,4-c]pyra-
zol-6-one (I) with hydrochloric acid at 25 C gives
rise to equilibrium between the lactone and the corre-
1
at 3135 cm arises from the dimer, and C H bond
gives rise to strong bands at 3040 cm and 945
( CH). Stretching vibrations of the C N
bond appear at 1625 1630 cm . The positions of the
1
1
930 cm
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

1044
TYUKHTENEVA, BADOVSKAYA
Scheme 2.
sponding hydroxy acid; the equilibrium takes 14 days
to establish, and the lactone conversion is 22%. At
70 C, no opening of the lactone ring occurs. Accord-
ing to the spectrophotometric data, the dihydropyra-
zole ring is completely converted into pyrazole in 1 h.
Evaporation of the hydrolyzate gave hydrochloride V
which was identical to a sample obtained in ethanol.
Under milder conditions (25 C), the transformation
of the dihydropyrazole ring in I occurs at a lower rate.
The isomerization of 4,5-dihydro-3H-pyrazole into
4,5-dihydro-1H-pyrazole was complete in 24 h, and
its oxidation to pyrazole required more than 14 days.
Thus the transformation of the dihydropyrazole ring
of compound I in aqueous medium at 25 C is accom-
panied by opening of the lactone ring. Evaporation of
the reaction mixture obtained by acid hydrolysis of
I at 25 C gave a mixture of products which we failed
to separate. Presumably, it contained bicyclic com-
pounds having a butanolide ring fused to 4,5-dihydro-
1H-pyrazole or pyrazole ring and hydroxy acids
having dihydropyrazole and pyrazole rings.
Alkaline hydrolysis of compound I is also accom-
panied by isomerization of 4,5-dihydro-3H-pyrazole
ring into 4,5-dihydro-1H-pyrazole and subsequent
transformation into pyrazole, as it occurred in the
acid hydrolysis. By acidification of the alkaline
hydrolyzate we succeeded in isolating 4-hydroxy-
methylpyrazole-3-carboxylic acid (VI). In this case,
opening of the butanolide ring precedes the trans-
formation of dihydropyrazole into pyrazole: Even
after 10 min, the titration data indicated complete
opening of the butanolide ring, whereas the trans-
formation of the dihydropyrazole ring into pyrazole
required 3 h under the same conditions.
methyl group because of overlap of OH and NH
1
absorptions above 3000 cm ; however, a broad band
1
at 3155 cm is likely to belong to stretching vibra-
tions of the associated NH group in the pyrazole ring,
1
and a strong broad band at 3280 cm may be attri-
buted to vibrations of the alcoholic hydroxy group
involved in hydrogen bond. The pyrazole ring in VI
gives rise to characteristic absorption bands at 3030,
1
1
960, and 800 cm (C H), 1660 cm (C N), and
1
1580 cm ( NH).
The presence of hydroxy and carboxy groups in
molecule VI was confirmed by appropriate test reac-
tions (decoloration of bromine and potassium per-
manganate in water and acid reaction of aqueous
solution). The molecular weight of compound VI
determined from the neutralization equivalent was 138
(calculated M 142).
EXPERIMENTAL
The IR spectra were recorded on a UR-20 instru-
ment. The UV spectra were measured on a Specord
UV-Vis spectrophotometer in ethanol and water. TLC
analysis was performed on Silufol plates using 20:1
dioxane water as eluent; spots were visualized by
treatment with iodine vapor, Bromophenol Blue, and
potassium permanganate.
2,6-Dihydro-4H-furo[3,4-c]pyrazol-6-one (III).
Dry chlorine, 0.49 l (0.022 mol), was passed over
a period of 30 min through a solution of 1.26 g
(0.01 mol) of compound I in chloroform. The solvent
was immediately distilled off on a water bath, and
the residue (0.97 g) was recrystallized from benzene.
2,6-Dihydro-4H-furo[3,4-c]pyrazol-6-one hydro-
bromide (IV). A solution of 1.60 g (0.01 mol) of
bromine in chloroform was added dropwise with stir-
ring to a solution of 1.26 g (0.01 mol) of compound I
in 100 ml of chloroform. The precipitate was filtered
off and washed with cold chloroform. Yield 1.7 g.
The IR spectrum of acid VI (mineral oil) contains
a strong absorption band at 1710 cm belonging to
1
stretching vibrations of the acid carbonyl group, and
stretching vibrations of the acid OH group appeared
1
as a set of bands in the region 2400 2700 cm . It
was difficult to identify absorption of the hydroxy-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

SUBSTITUTED BUTANOLIDES AND BUTENOLIDES: XVI.
1045
2,6-Dihydro-4H-furo[3,4-c]pyrazol-6-one hydro-
chloride (V). Concentrated hydrochloric acid, 1 ml,
was added to a solution of 1.26 g (0.01 mol) of com-
pound I in 50 ml of ethanol, and the mixture was
refluxed for 10 min on a water bath. The solution was
evaporated under reduced pressure, the residue was
ground with an equal volume of diethyl ether, and the
precipitate was filtered off. Yield 1.14 g, mp 142 C.
4-Hydroxymethylpyrazole-3-carboxylic acid
(VI). A solution of 1.26 g (0.01 mol) of compound I
in 20 ml of 20% aqueous NaOH (0.1 mol) was heated
for 3 h at the boiling point. The mixture was cooled,
acidified with dilute (1:1) hydrochloric acid to pH 1,
and saturated with sodium chloride. After 24 h, the
precipitate was filtered off and recrystallized from
aqueous ethanol. Yield 0.68 g.
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Kost, A.N. and Grandberg, I.I., Advances in Hetero-
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Clack, R.W., Aust. J. Chem., 1972, vol. 25, no. 6,
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geterotsiklicheskikh soedinenii, Moscow: Khimiya,
1966, pp. 319 397.
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