1,3,4,6-Tetracarbonyl compounds: IV. Reaction of 3,4-dihydroxy-2,4-hexadiene-1,6-diones with hydrazine and arylhydrazines

Article abstract of DOI:10.1023/A:1013431407273

Reactions of 1,6-disubstituted 3,4-dihydroxy-2,4-hexadiene-1,6-diones with hydrazine hydrate or hydrochloride afforded heterocyclization products, 3,3′-bipyrazoles. The chemoselective reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with arylhydrazines gave rise to 1,1′,5,5′-tetraaryl-3,3′-bipyrazoles and 1 ,5-diaryl-3-aroylacetylpyrazoles. The specific structural features of the pyrazole derivatives obtained are discussed. Some pyrazoles show bacteriostatic and antileukemic activity.

Full text of DOI:10.1023/A:1013431407273

Russian Journal of Organic Chemistry, Vol. 37, No. 10, 2001, pp. 1486 1494. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 10, 2001,
pp. 1555 1563.
,
,
,
Original Russian Text Copyright
2001 by Shironina, Igidov, Koz minykh, Kon shina, Kasatkina, Koz minykh.
1,3,4,6-Tetracarbonyl Compounds: IV.* Reaction
of 3,4-Dihydroxy-2,4-hexadiene-1,6-diones with Hydrazine
and Arylhydrazines
T. M. Shironina, N. M. Igidov, E. N. Koz,minykh, L. O. Kon,shina,
Yu. S. Kasatkina, and V. O. Koz,minykh,
Perm State Pharmaceutical Academy, Perm, 614051 Russia
Received December 1, 2000
Abstract Reactions of 1,6-disubstituted 3,4-dihydroxy-2,4-hexadiene-1,6-diones with hydrazine hydrate or
hydrochloride afforded heterocyclization products, 3,3 -bipyrazoles. The chemoselective reaction of
1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with arylhydrazines gave rise to 1,1 ,5,5 -tetraaryl-3,3 -
bipyrazoles and 1,5-diaryl-3-aroylacetylpyrazoles. The specific structural features of the pyrazole derivatives
obtained are discussed. Some pyrazoles show bacteriostatic and antileukemic activity.
Some terminally substituted 1,3,4,6-tetraketones I
were established to react with hydrazine, phenyl-
hydrazine, and p-nitrophenylhydrazine yielding
isomeric symmetrical with respect to the interring
bond C3 C3 and nonsymmetrical bipyrazoles II and
III [2 11]. In some cases were also isolated mono-
cyclic products, 3-acylpyrazoles IV [4, 11], or
mixtures of compounds I and IV [4] (Scheme 1).
It was assumed that the direction of the process
depended only on the amount of hydrazine brought
into the reaction. The structure of most pyrazoles was
established without application of the spectral
methods and thus up till now was not very convinc-
ing. In all the studies mentioned [2 11] the reaction
mechanisms were not considered.
The published data suggest that the primary
nucleophilic attack of hydrazines is not selective: It is
directed both at the external carbonyl group C1,6= O
of the -diketo fragment and at the internal carbonyl
C
3,4= O of the -oxounit in the initial tetraketones
I [4, 8, 11]. As evidence of the chemoselectivity in
reaction of 1,3,4,6-tetraketones with hydrazines is
considered formation in some cases of isomer mix-
tures of pyrazoles (see, e.g., [4]). This fact may be
understood in a way as participation in the reaction of
one among the tautomeric forms of 1,3,4,6-tetra-
ketones A C (Scheme 2) that are present in the solu-
tions of the compounds [1, 12] (as unambiguously
shows X-ray diffraction analysis in the solid state
exists only chelate structure B [1, 13 17]).
Scheme 1.
Some bipyrazoles II found application as ad-
ditives to scintillators [6] and in synthesis of heat-
resistant polymers [10]. Also short communica-
tions appeared on biological activity of pyrazoles II
and IV [11, 18]. The practical applications of these
products generated by reactions of 1,3,4,6-tetra-
ketones, and requirement of new isomeric pyrazoles
with new structures stimulated further studies of
reactions between tetracarbonyl synthons I and
hydrazines. We investigated reactions of 1,6-disub-
R1 = Me, Et, Ar, Het; R2 = H, C6H5, 4-NO2C6H4.
stituted
3,4-dihydroxy-2,4-hexadiene-1,6-diones
*
(Ia f) with hydrazine hydrate or hydrochloride in
For communication III see [1].
1070-4280/01/3710-1486$25.00 2001 MAIK Nauka/Interperiodica

1,3,4,6-TETRACARBONYL COMPOUNDS: IV.
1487
Scheme 2.
R = Alk
R = Alk, Ar
Scheme 3.
R = Ar
R = CH3 (a), C6H5 (b), 4-CH3C6H4 (c), 2,4-(CH3)2C6H3 (d), 4-ClC6H4 (e), 4-FC6H4 (f).
Scheme 4.
II, Ar2 = C6H5, Ar1 = C6H5 (g), 4-CH3C6H4 (h), 2,4-(CH3)2C6H3 (i), 4-ClC6H4 (j), 4-FC6H4 (k); Ar2 = 2-CH3C6H4,
Ar1 = C6H5 (l), 4-ClC6H4 (m); Ar1 = C6H5, Ar2 = 4-HOOCC6H4 (n); IV, Ar1 = C6H5, Ar2 = C6H5 (a),
2-CH3C6H4 (b); Ar1 = 4-ClC6H4, Ar2 = 2-CH3C6H4 (c); Ar1 = C6H5, Ar2 = 4-HOOCC6H4 (d).
ethanol, dioxane, or acetic acid. The reaction pro-
ceeds at short boiling of reagents mixture and dis-
regarding the ratio of the latter provides 5,5 -di-
products that basing on spectral data were assigned
structures 1,1 ,5,5 -tetraaryl-3,3 -bipyrazoles (IIg n)
and 3-aroyl-1,5-diarylpyrazoles (IVa d) [18 21]
substituted 3,3 -bipyrazoles IIa f [18 21] (Scheme 3). (Scheme 4).
Yields, melting points, and elemental analyses of
5,5 -Diaryl-substituted bipyrazoles IIb f form in high
yields, from 80 to 91%, but the yield of compound
IIa with methyl groups in 5 and 5 positions is con-
siderably lower, only 48%, due to notable tarring in
the reaction mixture characteristic of nucleophilic
reactions with 2,5-dihydroxy-3,5-octadiene-2,7-dione
(Ia). Unlike the reaction with hydrazine the treating
of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones
(Ib f) with equimolar amount or with double excess
of phenyl-, o-tolyl- or p-carboxyphenylhydrazine after
short boiling of the reagent mixture in acetic acid
depending on the reagents ratio afforded two reaction
compounds IIa n and IVa d are given in Table 1,
and their spectral characteristics are listed in Table 2.
The constants of the known compounds IIa, g, IVa
are consistent with the published data [2 4, 6]
(Table 1).
In the IR spectra of compounds II are observed the
bands at 1617 1590 and 1580 1543 cm 1 correspond-
ing to vibrations of C=C and C=N bonds in the
pyrazole and benzene rings. These bands are in good
agreement with the published data for the known
bipyrazoles [8, 11].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1488
SHIRONINA et al.
Table 1. Yields, melting points, and elemental analyses of pyrazoles IIa n, IVa d
Compd.
no.
Found, %
N (Hlg)
Calculated, %
N (Hlg)
Yield,a
%
mp,
(decomp.)
C
Formula
C
H
C
H
IIab
IIb
IIc
IId
IIe
48
91
80
85
85
278 279
320 321
>320
255 256
>320
59.69 6.52
75.14 5.37
76.13 6.29
76.86 6.31
61.20 3.85
33.80
18.94
18.17
16.75
15.36
(20.27)
16.92
C8H10N4
59.24 6.21
75.50 4.93
76.41 5.77
77.16 6.48
60.86 3.41
34.54
19.57
17.82
16.36
15.77
(19.96)
17.38
(11.79)
12.78
12.01
11.33
11.04
(13.97)
11.81
(8.01)
12.01
10.46
(13.24)
10.64
7.65
C18H14N4
C20H18N4
C22H22N4
C18H12Cl2N4
IIf
80
>320
66.47 4.23
C18H12F2N4
67.08 3.75
IIgc
IIh
IIi
68
50
61
50
233 234
217 218
283 284
234 235
81.84 4.77
82.51 6.12
83.07 5.75
71.39 4.41
13.12
11.78
11.64
10.68
(14.25)
11.32
C30H22N4
C32H26N4
C34H30N4
C30H20Cl2N4
82.17 5.06
82.38 5.62
82.56 6.11
71.01 3.97
IIj
IIk
42
204 205
75.22 4.86
C30H20F2N4
75.94 4.25
IIl
IIm
44
48
233 234
271 272
82.77 5.90
72.13 4.66
12.34
10.71
(13.59)
11.05
8.31
C32H26N4
C32H24Cl2N4
82.38 5.62
71.78 4.52
IIn
35
53
47
40
>300
72.68 4.49
79.34 4.70
79.36 5.71
66.46 3.78
C32H22N4O4
C24H18N2O2
C25H20N2O2
C25H18Cl2N2O2
72.99 4.21
78.67 4.95
78.93 5.30
66.83 4.04
IVad
IVb
IVc
162 163
169 170
175 176
7.12
5.84
7.36
6.23
(15.49)
7.25
(15.78)
6.83
IVd
61
183 184
73.27 4.63
C25H18N2O4
73.16 4.42
a
b
c
d
Yield of compounds IIa f is given for preparation by reaction of tetraketones I with hydrazine hydrate.
mp 286 C [3].
Yield 73% [6], mp 232 [2], 233 [4], 231 C [6].
mp 164 166.5 C [4].
1
In the H NMR spectra of bipyrazoles II recorded
characteristics of bipyrazoles IIa and IId are in a
satisfactory agreement with 1H NMR prediction
spectra calculated along the software of ACD/Labs
(see EXPERIMENTAL). Certain discrepancies
in DMSO-d6 alongside the signals from the protons
of substituents in 5 and 5 positions (Table 2)
appeared in a weak field at 6.58 7.05 ppm a
resonance from the methine proton located in 4 posi-
tion of the pyrazole ring.
The signal at 6.29 ppm from C4,4 H in the
1H NMR spectrum of compound IIa lacking con-
jugated benzene rings is an exception. In the spectra
of compounds IIb f appears also a broadened signal
of the proton attached to the nitrogen atom of pyr-
azole ring (13.10 13.45 ppm); the signal disappears
on addition of deutereted acetic acid CD3COOD. In
the spectrum of bipyrazole IIa this signal is observed
in a stronger field, at 12.68 ppm. The other signals
save that of NH group of the ring are not affected
with addition of deuteroacetic acid. The spectral
1
between the experimental and prediction H NMR
spectra (in the experimental spectrum the signal of
methine proton is shifted upfield as compared with
the predicted spectrum, and the peak of the proton at
the pyrrole nitrogen of the ring is on the contrary
shifted more downfield than in the predicted
spectrum) may be due to solvation in DMSO solu-
tion.
In the mass spectrum of bipyrazole IIl are present
a molecular ion peak of maximum intensity, fragment
ion peaks, for instance, that of nitrile F (m/z 259),
that of 3-pyrazole G (m/z 233), and also peaks of ions
derived from these fragment ions, e.g., of nitrile
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1,3,4,6-TETRACARBONYL COMPOUNDS: IV.
Table 2. H NMR spectra of pyrazoles IIa e, g i, k m, IVa d in solutions in DMSO-d6
1489
1
Compd. no.
Chemical shift, , ppm
IIa
IIb
IIc
IId
IIda
IIe
IIg
IIh
IIi
IIk
IIl
IIm
IVa
2.23 s (6H, CH3), 6.29 s (2H, CH), 12.68 br.s (2H, NH)
6.59 s (2H, CH), 6.92 7.80 m (10H arom), 13.10, 13.37 br.s (2H, NH)
2.30 s (6H, CH3), 6.58 s (2H, CH), 7.00 7.75 m (8H arom), 13.30, 13.45 br.s (2H, NH)
2.32 s (6H, o-CH3), 2.42
s (6H, p-CH3), 6.76 s (2H, CH), 7.11, 7.42 m (6H arom), 13.12, 13.25 br.s (2H, NH)
2.32 s (6H, o-CH3), 2.43 s (6H, p-CH3), 6.77 s (2H, CH), 7.08, 7.11, 7.13, 7.42, 7.45 (6H arom)
6.65 s (2H, CH), 7.05 7.85 m (8H arom), 13.30, 13.42 br.s (2H, NH)
7.01 s (2H, CH), 7.19 7.50 m (20H arom)
2.32 s (6H, CH3), 7.06 s (2H, CH), 7.17 7.41 m (18H arom)
2.28 s (6H, CH3), 2.50 s (6H, CH3), 6.95 s (2H, CH), 7.03 7.28 m (16H arom)
7.03 s (2H, CH), 7.20 7.42 m (18H arom)
2.03 s (6H, CH3), 7.01 s (2H, CH), 7.15 7.58 m (18H arom)
1.96 s (6H, CH3), 7.05 s (2H, CH), 7.28 7.51 m (16H arom)
4.80 s (2H, CH2, form Db, 40%), 7.02 s (1H, CH of pyrazole), 7.15 c (1H, CH, form Eb, 60%), 7.25 7.68,
8.02 8.08 (15H arom), 16.45 br.s (1H, OH, form Eb)
IVb
IVc
IVd
1.96 s (3H, CH3), 7.01 s (1H, CH), 7.10 7.95 m (14H arom)
1.93 s (3H, CH3), 6.95 s (1H, CH), 7.22 8.14 m (12H arom)
6.93 s (1H, CH), 7.25 7.96 m (14H arom), 12.73 s (1H, OH)
a
b
Spectrum registered in a mixture DMSO-d6 CD3COOD, internal reference TMS.
See Scheme 4.
fragments [C6H5C N C6H4CH3-2]+ (m/z 194) and
[C6H5C N] (m/z 103). These data fully confirm the
structure of compounds II obtained and are well
consistent with the known data on fragmentation of
pyrazole derivatives at electron impact [22].
Since in the mass spectrum of compound IIl are
present peaks of fragment ions F and G with m/z 259
and 233, and also a peak of N-o-tolylbenzonitrile ion
(m/z 194) the possible isomeric structures with axial
symmetry along the C3 C3 bond of 2,2 ,5,5 -tetra-
aryl-3,3 -bipyrazoles VII and nonsymmetrical bi-
pyrazoles III (R1 = R2 = Ar, Scheme 1) should be
rejected.
0
Analysis of spectra of mass-ion series [24] of
bipyrazoles II shows that as a rule the most abundant
are the ions of the first and second homologous
groups including pyrazole and nitile ions. The high
selectivity of fragmentation (N = 1 or 2), high or
maximum intensity of the molecular ion peak along-
side with low intensity of the fragment ions of
pyrazole, the selective rupture of the N N bond in the
ring, the stability of the corresponding pyrazole ions,
all these data are in conformity with published data
on pyrazole derivatives decomposition under electron
impact [22, 25] and also evidence the correct assign-
ment of the structure to compounds II.
This set of fragment ions, first of all ions [1/2M]
0
formed from bipyrazoles II, permits to exclude the
alternative structures pyridazino[4,3-c]pyridazines
V and VI (Scheme 5) although their formation could
not have been considered improbable basing on the
published data [23].
Scheme 5.
In the IR spectra of pyrazoles IV is present a broad
absorption band at low frequencies corresponding to
stretching vibrations of carbonyl groups in the -di-
1
ketone moiety in the 1610 1565 cm region evidenc-
ing that in the solid state in the molecule exists an
OH-chelate cycle with an intramolecular hydrogen
bond of O H O = C < type (form E) [26]. Yet in
1
R = H, Ar.
the H NMR spectrum of compound IVa recorded in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1490
SHIRONINA et al.
DMSO-d6 solution alongside the methine proton
signal of the enolized benzoylacetyl fragment at
7.15 ppm and the broadened signal of the hydroxy
proton from enol at 16.45 ppm appears also the CH2
group signal at 4.80 ppm (Table 2) indicating that
both keto-enol form E and -diketone tautomer D are
present in the solution; the fraction of the latter
amounts to 40%.
dienol chain form of 1,3,4,6-tetraketones B into reac-
tion with nucleophiles [18, 21, 30]. In reaction with
hydrazine takes part just the dienol tautomer B of
1,3,4,,6-tetraketones and not the ring form C present
in the solution. In the latter case the nucleophilic
attack of hydrazine should be directed at the C5 atom
of the ring that according to the quantum-chemical
calculations is the most probable site for attack in the
nucleophilic reactions with charge and orbital control
where the substrates are 2-hydroxy-2,3-dihydro-3-
furans [31]. The formation of monopyrazole IV and
not the alternative compounds III, VII, or IX
unambiguously proves the proposed reaction scheme.
The spectral data indicate that compounds IV
cannot have a structure of 3-aroylmethyl-1,6-diaryl-
1H-4-pyridazinones (VIII); their formation could not
be excluded a priori (Scheme 6). Thus in the IR
spectra of compounds IV no carbonyl group bands
1
1
appear at higher frequencies than 1610 cm ; however
It should be mentioned that in the H NMR spectra
according to published data the absorption band of
carbonyl C4= O stretching vibrations in the IR spectra
of 1H-4-pyridazinones VIII is observed at the
of a number of initial 1,3,4,6-tetraketones I whose
spectra were measured for the first time we revealed
several tautomeric forms in equilibrium. For instance,
in the spectrum of solution of 4,5-dihydroxy-3,5-
octadiene-2,7-dione (Ia) in DMSO-d6 are present
4 forms (Scheme 2): a dienol chain form B (R =
CH3), 36%, ring form 2-hydroxy-2,3-dihydro-3-
furanone C (R =CH3), 59%, and two minor chain
tautomers: detected for the first time ketoenol H
(R = CH3), 4%, and traces of keto form A (R =
CH3), about 0.6%. However in deuterochloroform
the spectrum of compound Ia is significantly less
complicated: the predominant form is dienol B (R =
CH3), 96%, and a minor isomer A (R = CH3), 4%
(see EXPERIMENTAL).
1
frequency no less than 1616 cm [27] and most often
1
at 1639 1630 cm [27 29].
In the mass spectrum of compound IVc are
present the peaks of the fragment ion [4-ClC6H4 C
N C6H4CH3-2]+ (m/z 228, 230), that are not
consistent with a structure of the corresponding
5- aroylacetyl-1,3-diarylpyrazole (IX) (Scheme 6).
Scheme 6.
R = Ar.
Besides in the spectrum were lacking peaks of ions
[4-ClC6H4CO CH2CO C N C6H4CH3-2]+
(m/z
R = CH3, 2,4-(CH3)2C6H3.
298, 300) and [4-ClC6H4 C N NHC6H4CH3-2]+
(m/z 243, 245) that would form at fragmentation of
the corresponding derivative IX.
1H NMR spectrum in DMSO-d6 of 1,3,4,6-tetra-
ketone Id containing two o,p-dimethylphenyl sub-
stituents at both ends of the chain showed the pres-
ence of only two tautomers: dienol form B [R = 2,4-
(CH3)2C6H3)], 10%, and prevailing cyclic semiacetal
C [R = 2,4-(CH3)2C6H3], 90% (Scheme 2). The
spectrum of compound Id demonstrated the absence
of the chain ketone form A [R = 2,4-(CH3)2C6H3]
and monoenol H [R = 2,4(CH3)2C6H3]. The spectra
are consistent with the known data on the presence in
DMSO solutions of 1,6-disubstituted 1,3,4,6-tetra-
ketones of open-chain and cyclic tautomers with pre-
valence of the latter [1, 12, 32]. However in contrast
to the above mentioned example in deuterochloroform
Apparently the reaction of 1,6-disubstituted
3,4-dihydroxy-2,4-hexadiene-1,6-diones
I
with
hydrazine and arylhydrazines occurs regioselectively
with primary addition of the latter to enolized
carbonyl group = C 3 O H or = C 4 O H with equal
probability when in positions 1 and 6 of bichelate B
are the same substituents R. Further the arising
monoenhydrazinocarbonyl intermediate undergoes
heterocyclization into the corresponding 3-acyl deriv-
atives of pyrazole IV or in the presence of excess
hydrazine into bipyrazoles II. This scheme is fully
consistent with the current views on involving the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1,3,4,6-TETRACARBONYL COMPOUNDS: IV.
1491
1
the H NMR spectrum showed the presence of the
water solution of sodium carbonate till neutral. The
solvent was evaporated till dryness, the residue was
recrystallized from ethanol. We obtained colorless
crystals of compound Ia. Yield 5 g (29%). mp 119
120 C (publ.: 120 121 C [3, 4, 34], 123 C [37]).
1H NMR spectrum (CDCl3), , ppm: 2.25 s (6H,
CH3), 3.93 s [4H, CH2, keto form A, 4% (Scheme 2)],
6.38 s (2H, CH, enol form B, 96%), 13.85 br.s (2H,
OH, form B). 1H NMR spectrum (DMSO-d6), , ppm:
2.17 s [3H, C5CH3, form C (Scheme 2)], 2.22 s (6H,
CH3, form B), 2.28 s (3H, CH3COCH2, form C),
sole dienol tautomer B (see EXPERIMENTAL) also
in agreement with the published data on the spectra of
1,6-diaryl-1,3,4,6-tetraketones [32].
Preliminary studies indicate that bipyrazoles II
possess bacteriostatic activity with respect to
Staphylococcus aurous and Escherichia coli [18, 30].
Bipyrazoles IIb, d, e, g were tested for antitumor and
anti-AIDS activity.
activity was revealed in compound IId.
A pronounced antileukemic
2
2.78 d, 2.90 d (2H, CH2COCH3, J 14.0 Hz, form
EXPERIMENTAL
C, 59%), 3.88 s (1H, CH2, form A, 0.6%), 3.97 s
[1H, CH2, form H, 4% (Scheme 6)], 5.39 s (1H,
C4H, form C), 6.23 s (1H, CH, form H), 6.37 s (1H,
CH, form B, 36%), 7.63 s (1H, C2OH), form C).
Mass spectrum, m/z (Irel, %) (peaks presented have
IR spectra of compounds II and IV were recorded
on spectrophotometers UR-20, Specord M-80, and
Phillips Analytical PU9716 IR from mulls in mineral
1
oil. HNMR spectra of compounds I, II, and IV were
Irel > 2%): 170 (3) M
0
, 142 (2) [M CO]
0
, 127 (17)
, 86 (3),
registered on spectrometers RYa-2310 (60 MHz),
Bruker AM-300 and Varian VXP-300 (300 MHz)
from solutions in deuterochloroform, DMSO-d6 or a
mixture of DMSO-d6 with CDCl3. Internal reference
TMS or HMDS. 13C NMR spectra of compounds II
were measured on JEOL EX90A FT-NMR instru-
ment at operating frequency 22, 30 MHz from solu-
tions in DMSO. Mass spectra of compounds I, II,
and IV were obtained on Kratos MS-30 instrument
(Great Britain) in direct input mode, emission cur-
rent 1000 mA, ionizing electrons energy 70 eV,
evaporator temperature 120 150 C. The prediction
NMR spectra were constructed with the use of a
routine from ACD/Labs Software Co (Toronto,
Canada, http://www.acdlabs.com). The calculations
did not take into account the solvation effects. The
homogeneity of compounds was proved by TLC on
Silufol UV-254 plates, eluent benzene ether acetone,
10: 9: 1, development in iodine vapor. The known
initial 1,3,4,6-tetraketones Ia e were prepared by
Claisen condensation of methyl ketones with diethyl
oxalate in the presence of sodium ethylate [1, 2, 6,
33 36].
[M CH3CO]+ , 109 (2) [M CH3CO H2O]
0
85 (100) [CH3COCH2C O]+ , 71 (2), 69 (8)
[O=C=CH C O]+ , 55 (6), 53 (3), 45 (2), 43
[CH3CO]+ , 41 (10), 40 (29), 33 (28). The fragment-
ation character of compound Ia under the electron
impact is well consistent with the known scheme of
degradation of 1,6-diaryl-1,3,4,6-tetraketones under
such conditions [38]. Found, %: C 56.47; H 5.92.
C8H10O4. Calculated, %: C 56.79; H 6.23.
1,6-Bis(2,4-dimethylphenyl)-3,4-dihydroxy-2,4-
hexadiene-1,6-dione (Id). To 100 ml of methanol
was added by small portions 4.6 (0.2 mmol) of
sodium, then methanol was distilled off till dryness,
the sodium methylate was ground into powder and
charged into a flat-bottom flask, and 150 ml of ether
was added thereto. Then at cooling and stirring was
added dropwise a mixture of 14.6 g (0.1 mol) of
diethyl oxalate and 29.6 g (0.2 mol) of 2 ,4 -di-
methylacetophenone. On the next day the dry residue
was thoroughly mixed with 100 ml of hot water and
at stirring concn. HCl was added till pH 3 4. The
precipitate was washed with water and ethanol and
recrystallized from dioxane. Yield 19.6 g (56%). mp
160 161 C (publ.: 169 170 C [35]). 1H NMR
spectrum (CDCl3), , ppm: 2.37 s (6H, o-CH3),
2.58 s (6H, p-CH3), 6.88 s (2H, CH), 7.12 s, 7.27 s,
7.62 s, 7.66 s (6H arom), 15.43 s (2H, OH); 100%
4,5-Dihydroxy-3,5-octadiene-2,7-dione (Ia). To
100 ml of methanol preliminary distilled from sodium
metal was added by portions 4.6 g (0.2 mmol) of sod-
ium, then methanol was distilled off till dryness, and
to sodium methylate thus obtained was added 150 ml
of anhydrous ethyl ether. Then at cooling and stirring
was added dropwise a mixture of 14.6 g (0.1 mol) of
diethyl oxalate and 11.6 g (0.2 mol) of acetone. On
the next day the solid residue was dissolved in 40 ml
of water, and by portions while stirring was added
10% aqueous hydrochloric acid till pH 3 4. The reac-
tion product was extracted into ether (3 50 ml), the
extracts were combined, and washed with a saturated
1
of dienol form B (Scheme 2). H NMR spectrum
(DMSO-d6), , ppm: 2.22 s, 2.30 s, 2.33 s, 2.39 s,
2.50 s (12H, 4CH3), 3.47 d, 3.69 d [2H, CH2COAr,
2J 17.5 Hz, form C (Scheme 2)], 5.97 s (1H, C4H,
form C, 90%), 6.91 s (1H, CH, form B, 10%),
7.06 s, 7.11 s, 7.13 s, 7.17 s, 7.45 s, 7.48 s, 7.69 s,
7.72 s (6H arom), 7.85 br.s (1H, C2OH, form C).
C22H22O4.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1492
SHIRONINA et al.
1, 6-Bis(p-fluorophenyl)-3, 4-dihydroxy-2,4-
133.38 4.7, 134.23 0.2, 135.09 2.5, 135.28 5.8,
137.07 0.6, 141.44 1.5 (C arom), 139.10 4.9
(C3), 145.55 2.4 (C5), 146.18 12.7 (C3 ), 148.03
2.5 (C5). Mass spectrum, m/z (Irel, %) (peaks
presented have Irel > 5%): 343 (23) [M+1]+ , 342
hexadiene-1,6-dione (If) was prepared as compound
1
Id. Yield 16.2 g (49%). mp 204 205 C. H NMR
spectrum (DMSO-d6), , ppm: 3.52 d, 3.85 d [2H,
2
CH2COAr, J 16.0 Hz, form C (Scheme 2)], 6.37 s
(1H, C4H, form C, 77%), 7.26 7.40 s, 7.86 8.03 s
(9H, CH, 8H arom). C18H12F2O4.
(97) M , 341 (21), 226 (5), 198 (15) [I], 171 (25)
0
[1/2M]+ [J], 170 (6), 163 (9), 156 (12), 154 (6), 151
(5), 148 (8), 146 (16), 145 (100) [1/2M C N]+ , 144
5,5 -Disubstituted
3,3 -bipyrazoles
IIa f.
(43) [1/2M HCN] , 143 (10), 142 (7), 141 (11), 131
0
General procedure. To a solution of 0.004 mol of an
appropriate 1,3,4,6-tetraketone Ia f in 30 70 ml of
dioxane, ethanol, or acetic acid was added at stirring
0.2 ml (nearly 1 equiv) or 0.5 ml (excess) of 70%
water solution of hydrazine or 0.84 g (0.008 mmol)
of hydrazine hydrochloride, and the mixture was
boiled for 10 20 min. The precipitate was filtered off
and recrystallized from dioxane, acetic acid, or
benzene; or the solvent was evaporated, and the
residue was recrystallized from dioxane or benzene.
(23), 130 (70) [1/2M C N CH3]+ , 129 (10)
[1/2M HCN CH3]+ , 128 (14), 127 (7), 117 (8), 116
(9), 114 (16), 105 (8) [2,4-(CH3)2C6H3]+ , 103 (6),
91 (8), 88 (13), 79 (6), 77 (12).
5,5 -Dimethyl-3,3 -bipyrazole (IIa). Yield 0.3 g
(48%). mp 278 279 C (decomp.) (publ.: 286 C [3]).
1H NMR spectrum (DMSO-d6), , ppm: 2.23 s (6H,
CH3), 6.29 s (2H, CH), 12.68 br.s (2H, NH).
Further are given for comparison the data of predic-
1
tion H NMR spectrum, , ppm: 2.33 s (6H, CH3),
5,5 -Bis(p-chlorophenyl)-3,3 -bipyrazole (IIf).
6.11 s (2H, CH), 11.88 br.s (2H, NH). 13C predic-
tion spectrum, C, ppm: 11.82 1.7 (CH3), 11.99
2.1 (CH3), 103.72 3.3 (C4), 103.83 3.3 (C4 ),
140.13 4.5 (C3), 140.50 1.0 (C5), 145.98 12.7
Yield 1.2 g (85%). mp >320 C (decomp.). IR spec-
1
trum, , cm : 3220 (NH), 1617, 1565, 1533, 1495,
1465, 1382, 1351, 1168, 1102, 1057, 978, 834, 793.
13C NMR spectrum (DMSO-d6): 100.08 (C4, C4 ),
126.92, 127.88, 128.85, 129.24, 132.15, 135.90
(C arom), 141.45 (C3, C3 ), 143.16 (C5, C5 ). Further
are given for comparison the data of prediction
13C NMR spectrum, C, ppm: 100.68 (C4), 107.22
(C4 ), 125.55, 128.14, 128.18, 129.64, 130.50,
131.52, 132.55, 136.01 (C arom), 143.48 (C3 ),
145.38 (C3), 145.66 (C5), 146.87 (C5 ). Mass
(C3 ), 147.01
6.1 (C5 ).
5,5 -Bis(p-tolyl)-3,3 -bipyrazole (IIc). Yield 1 g
(80%). mp >320 C (decomp.). 13C NMR spectrum
(DMSO-d6), C, ppm: 20.65 (CH3), 99.24 (C4, C4 ),
125.00, 126.80, 127.86, 128.47, 129.47, 136.08
(C arom), 137.10 (C3, C3 ), 141.20 (C5, C5 ).
5,5 -Bis(2,4-dimethylphenyl)-3,3 -bipyrazole
(IId). Yield 1.15 g (85%). mp 255 256 C (decomp).
1H NMR spectrum (DMSO-d6), , ppm: 2.32 s (6H,
o-CH3), 2.42 s (6H, p-CH3), 6.76 s (2H, CH),
7.11 m, 7.42 m (6H arom), 13.12 br.s, 13.25 br.s
(2H, NH). Further are given for comparison the data
spectrum, m/z (Irel, %): 359 (4) [M+4]
[(M+4) H]+ , 357 (14) [M+2]+ , 356 (72)
[(M+2) H]+ , 355 (31) M , 354 (100) [M H]+ , 345
0
, 358 (15)
0
(2), 343 (5), 341 (6), 325 (6), 322 (2), 320 (7), 293
(3), 291 (13), 230 (1), 228 (3), 226 (9), 224 (6), 181
(4), 179 (3) [1/2(M+2)]+ , 177 (6) [1/2M]+ , 164 (3),
162 (6), 153 (6), 150 (3), 148 (6), 146 (9), 139 (6),
138 (12), 131(9), 127 (9), 119 (7), 113 (8), 111 (9)
[p-ClC6H4]+ , 106 (6), 105 (12), 102 (9), 101 (6), 91
(11), 89 (7), 77 (6), 76 (11) [C6H5]+ , 74 (8), 69 (18),
57 (16), 56 (11), 55 (9), 51 (11), 50 (6).
1
of prediction H NMR spectrum, , ppm: 2.32 s (6H,
o-CH3), 2.36 s (6H, p-CH3), 6.97 s, 7.06 s, 7.09 s,
7.41 s, 7.52 s (6H arom), 7.95 s (2H, C4H), 8.68
br.s (2H, NH). 13C NMR spectrum (DMSO-d6),
,
ppm: 20.52 (CH3), 102.50 (C4, C4 ), 126.12, 128.0C7,
131.86 (C arom), 134.93 (C3, C3 ), 137.22 (C5, C5 ).
Further are given for comparison the data of predic-
tion 13C NMR spectrum, C, ppm: 19.43 0.6,
1, 1 -5, 5 -Tetraaryl-3,3 -bipyrasoles IIg n).
General procedure. To a solution of 0.002 mol of an
appropriate 1,3,4,6-tetraketone Ib f in 20 ml of acetic
acid was added 0.004 mol of phenylhydrazine,
o-tolylhydrazine, or p-carboxyphenylhydrazine, and
20.90 0.1,
20.93 0.3
(CH3),
101.03 3.2,
107.92 3.0 (C4, C4 ), 125.06 0.4, 127.45 0.3,
129.20 0.5, 130.16 0.6, 130.58 1.2, 132.18 1.6,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1,3,4,6-TETRACARBONYL COMPOUNDS: IV.
1493
the mixture was boiled for 5 10 min. The precipitate
was filtered off and recrystallized from benzene or a
mixture dioxane hexane, 1: 1.
[C6H5C N C6H5]+ , 165 (7), 131 (6), 116 (14), 106
(11), 105 (94) [C6H5C O]+ , 104 (8), 89 (8), 78 (7),
77 (74) [C6H5]+ .
1,1 ,5,5 -Tetraphenyl-3,3 -bipyrazole
(IIg).
Yield 0.6 g (68%). mp 233 234 C (decomp.). IR
1
spectrum, , cm : 1592, 1543, 1497, 1445. Mass
spectrum, m/z (Irel, %) (peaks presented have Irel
>
5%): 439 (27) [M+1]+ , 438 (77) M
, 437 (29)
0
[M 1]+ , 334 (18) [M C6H5 HCN]+ , 219 (18)
[1/2M]+ [J], 204 (5), 192 (7), 190 (7), 180 (30)
1-o-Tolyl-3-(p-chlorobenzoylacetyl)-5-p-
chlorophenylpyrazole (IVc). Yield 0.35 g (40%).
mp 175 176 C. Mass spectrum, m/z (Irel, %) (peaks
presented have Irel > 5%): 452 (10), 450 (51), 448
(73) (peaks ratio 14: 70: 100) [M] , 311 (17), 309
0
(45) [M p-ClC6H4CO]+ , 297 (16), 295 (50) [M p-
ClC6H4COCH2]+ [C], 269 (6), 267 (15) [R], 230 (7),
228 (11) [p-ClC6H4 C N C6H4CH3-o]+ , 183 (36),
181 (100) [p-ClC6H4 COCH2C O]+ , 141 (21), 139
(63) [p-ClC6H4 C O]+ , 113 (8), 111 (21)
[p-ClC6H4]+ , 69 (57) [O=C=CH C O]+ .
[C6H5C N C6H5]+ , 165 (11), 152 (5), 116 (5),
105 (6) [C6H5CH=NH] , 102 (6), 91 (9), 89 (11),
0
78 (9), 77 (100) [C6H5]+ , 65 (5), 51 (38).
1,1 -Bis(o-tolyl)-5,5 -diphenyl-3,3 -bipyrazole
(IIl). Yield 0.4 g (44%). mp 233 234 C (decomp.).
Mass spectrum, m/z (Irel, %) (peaks presented have
The authors are grateful to Maybridge Chemical
Company (Great Britain) for assistance in recording
and interpretation of some IR and NMR spectra.
Irel > 5%): 466 (100) M , 259 (10) [L], 233 (17)
0
[1/2M]+ [M], 194 (11) [C6H5C N C6H4CH3-o]+ ,
128 (10) [C6H5C C C NH]+ , 105 (24) [o-
CH3C6H4N]+ , 103 (6) [C6H5C N]
0
,
91 (20)
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