Chemistry of diazopolycarbonyl compounds: VIII. Synthesis of nitrogen-containing heterocycles via transformations of substituted 2-diazopentane-1,3,5-triones

Article abstract of DOI:10.1023/B:RUJO.0000013140.10977.7f

Ethyl 5-aryl-2-diazo-3,5-dioxopentanoates and 1,5-diaryl-2-diazopentane-1, 3,5-triones are partially enolized in solutions. By O-methylation of enol forms of diazo esters with diazomethane ethyl 5-aryl-2-diazo-5-methoxy-3-oxopent-4- enoates were prepared. Concurrently with the O-methylation the diazo esters undergo heterocyclization into 3,5-disubstituted 4-hydroxypyrazoles which under the reaction condition suffer O- and N-methylation by excess diazomethane. 3,5-Diaroyl-4-hydroxypyrazoles were also obtained from diazopentanetriones but here triethylamine served as the cyclization reagent.

Full text of DOI:10.1023/B:RUJO.0000013140.10977.7f

Russian Journal of Organic Chemistry, Vol. 39, No. 11, 2003, pp. 1644 1648. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 11, 2003,
pp. 1713 1717.
Original Russian Text Copyright
2003 by Kutkovaya, Vyaznikova, Zalesov.
Chemistry of Diazopolycarbonyl Compounds: VIII.* Synthesis
of Nitrogen-containing Heterocycles via Transformations
of Substituted 2-diazopentane-1,3,5-triones
N. V. Kutkovaya1, N. G. Vyaznikova1, and V. V. Zalesov2
1Research Institute of Vaccines and Serum at Federal State Unitary Enterprise Biomed , Perm, Russia
2Perm State University, Perm, 614600 Russia
Received August 16, 2002
Abstract Ethyl 5-aryl-2-diazo-3,5-dioxopentanoates and 1,5-diaryl-2-diazopentane-1,3,5-triones are
partially enolized in solutions. By O-methylation of enol forms of diazo esters with diazomethane ethyl
5-aryl-2-diazo-5-methoxy-3-oxopent-4-enoates were prepared. Concurrently with the O-methylation the diazo
esters undergo heterocyclization into 3,5-disubstituted 4-hydroxypyrazoles which under the reaction con-
dition suffer O- and N-methylation by excess diazomethane. 3,5-Diaroyl-4-hydroxypyrazoles were also
obtained from diazopentanetriones but here triethylamine served as the cyclization reagent.
A general procedure was developed formerly for
aroylacetylation of diazocarbonyl compounds with
aroylketenes generated by thermal decarbonylation
of 5-aryl-2,3-dihydrofuran-2,3-diones Ia e [2 5].
Aroylketenes acetylate aroyldizomethanes [2],
adamantanoyldiazomethanes [3], ethyl diazoacetate
[4], and alkyl 3-diazo-2-oxopropanoates [5] affording
respectively 1,3-diaryl-2-diazopentane-1,3,5-triones
[2], 1-(1-adamantyl)-5-aryl-2-diazopentane-1,3,5-tri-
ones [3], ethyl 5-aryl-2-diazo-3,5-dioxopentanoates
[4], and alkyl 6-aryl-3-diazo-2,4,6-trioxohexanoates
[5]. It was shown [3 5] that these diazopolycarbonyl
compounds treated with triethylamine or primary
amines were capable to undergo cyclization affording
pyrazole derivatives, and under treatment with tri-
phenylphosphine ethyl 5-aryl-2-diazo-3,5-dioxo-
pentanoates furnished pyridazine derivatives [6, 7].
We carried on the research in the field of cyclization
of polycarbonyl diazo compounds proceeding under
mild conditions without nitrogen liberation from the
diazo group.
The IR spectra of compounds IIIi o are well
consistent with those of diazopentanetriones of similar
structure [4].
In the mass spectrum of compound IIIm the mol-
ecular ion peak is lacking, and appear peaks of the
Scheme 1.
First of all we performed acylation of ethyl di-
azoacetate and aroyldiazomethanes with aroylketenes
by procedures [2 4] and obtained already described
compounds IIIa h and previously unknown com-
pounds IIIi o: ethyl 5-aryl-2-diazo-3,5-dioxopenteno-
ates IIIa e, 1,5-diaryl-2-diazopentane-1,3,5-triones
IIIf o (Tables 1, 2, Scheme 1).
I), R = H (a), CH3 (b), CH3O (c), Cl (d), Br (e); III,
R = H5C2O, R = H (a), CH3 (b), CH3O (c), Cl (d),
Br (e); R = C6H5, R = H (f), CH3 (g), Cl (h), Br(i);
R = 4-O2NC6H4, R = H (j), CH3O (k), Cl (l), Br
(m); R =4-CH3C6H4, R = CH3O (n); R
4-BrC6H4, R = CH3O (o).
=
*
Communication VII see [1].
1070-4280/03/3911-1644$25.00 2003 MAIK Nauka/Interperiodica

CHEMISTRY OF DIAZOPOLYCARBONYL COMPOUNDS: VIII.
Table 1. Yields, melting points, and IR spectra of compounds IIIi o
1645
1
Compd. no.
Yield, %
mp,
C
IR spectrum, , cm (in mineral oil)
IIIi
73.8
22.4
32.9
49.4
63.9
48.5
66.0
96 98
2107 (N2), 1605, 1696 (C=O)a
IIIj
IIIk
IIIl
IIIm
IIIn
IIIo
123 124
138 140
140 142
143 145
117 118
132 135
2123 (N2), 1635, 1627 (C=O)
2128 (N2), 1653, 1635, 1628 (C=O), 2127 (N2), 1653, 1635 (C=O)a
2127 (N2), 1628, 1624 (C=O)
2125 (N2), 1628, 1624 (C=O)
2131 (N2), 1628, 1624 (C=O)
2131 (N2), 1628, 1624 (C=O), 2129 (N2), 1625, 1602 (C=O)a
a
Spectra registered from KBr pellets.
Table 2. Parameters of 1H NMR spectra of compounds IIIa, b, d, e, i, m, n in DMSO-d6, , ppm
Compd.
no.
COCH2CO, =CH, s H arom,
OH,
br.s
Ratio
enol ketone
a
CH3, CH2
s
m
IIIa
IIIb
1.31 t (3H, CH3), 4.31 q(2H, CH2), 1.15
(3H, CH3), 4.15 q (2H, CH2)
1.32 t (3H, CH3), 4.32 q (2H, CH2), 2.40 s (3H,
CH3C6H4), 1.19 t (3H, CH3), 4.18 (2H, CH2),
2.40 s (3H, CH3C6H4)
1.35 t (3H, CH3), 4.30 q (2H, CH2), 1.19 t (3H,
CH3), 4.17 q (2H, CH2)
1.35 t (3H, CH3), 4.30 q (2H, CH2), 1.28 t (3H,
CH3), 4.26 q (2H, CH2)
t
4.62
4.49
7.12
7.08
7.70
7.55
53: 47
54: 46
15.50
15.35
IIId
IIIe
4.43
4.52
7.10
7.19
7.75
7.80
79: 21
62: 38
IIIib
4.59
4.56
4.51
7.16
7.19
7.09
7.75
7.80
7.50
64: 36
78: 22
76: 24
IIImb
IIInb
2.47 s (3H, CH3C6H4), 3.86 s (3H, CH3OC6H4),
2.44 s (3H, CH3C6H4), 3.92 s (3H, CH3OC6H4)
a
Two sets of aliphatic protons signals correspond respectively to enol and keto forms.
The spectra were registered in mixed solvent, DMSO-d6 CCl4, 1: 3.
b
fragment ions [m/z (Irel, %)]: 389/387 (73/92) [M
(Table 2). In the spectra of compounds IIIa, d, i, m,
n the signal of enol hydroxy proton was not revealed
evidently because of its considerable broadening. Just
the existence of both forms in solutions of compounds
III governs the features of their chemical behavior.
N2]+ , 185/183 (75/88) [BrC6H4CO]+ , 150 (100)
[O2NC6H4CO]+ . In the mass spectrum of compound
IIIn also are present peaks of fragment ions [m/z (Irel,
%)]: 308 (64) [M N2]+ , 280 (18) [M N2 CO]+ ,
177 (48) [CH3OC6H4COCH2CO]+ , 135 (100)
[CH3OC6H4CO]+ , 119 (62) [CH3C6H4CO]+ , 91 (43)
[CH3C6H4]+ in conformity with the assumed struc-
ture.
It was reported in [3, 4] on intramolecular cycliza-
tion of diazoesters IIIa d and diazopentanetriones
IIIf, h into pyrazole derivatives induced by organic
bases, e.g., by triethylamine. We studied reactions of
diazo compounds IIIa e, i m, o with a nucleophile
like diazomethane and established that in reaction
with diazomethane according to TLC data formed a
complex mixture of products whose composition and
structure depended on the reaction conditions.
1
According to H NMR spectra described in [3, 4]
diazo compounds IIIa h were completely enolized in
CCl4 and CH2Cl2 solutions and existed in A form
with an intramolecular hydrogen bond of H-chelate
1
type. We registered H NMR spectra of compounds
For instance, in reactions of diazoesters IIIa e
and diazoketones IIIi m, o with an equimolar amount
of dizomethane in ethyl ether at 5 0 C from the
reaction mixture were isolated respectively 5-aroyl-4-
IIIa, b, d, e, i, m, n and found that in DMSO-d6
solution both enol (A) and -diketo (B) forms were
present.
Therewith the content of the latter depended on the
character of R -substituent and varied from 21 to 47%
hydroxy-3-ethoxycarbonylpyrazoles
IVa e
and
3,5-diaroyl-4-hydroxypyrazoles IVf k (Scheme 2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1646
STEPANOVA et al.
Table 3. Yields, melting points, IR and 1H NMR spectra of compounds IVe k, Va c, VIa c
Compd. Yield,
1
mp,
C
IR spectrum, , cm
1H NMR spectrum, , ppma
no.
%
67b
68
62
60
35
38
83
IVe
216 217 3329, 3196 (NH, OH), 1676 1.42 t (3H, CH3), 4.40 q (2H, CH2), 7.68 d (2H, C6H4),
(COOC2H5), 1628 (C=O) 7.88 d (2H, C6H4), 9.39 s (1H, NH), 14.11 s (1H, OH)
271 273 3200 sh, 3159 (NH, OH), 7.80 m (9H, C6H5, C6H4), 9.85 s (0.5H, NH), 10.08 s
1632, 1608 (C=O) (0.5H, NH), 14.25 s (1H, OH)
295 296 3322, 3211, 3184 (NH, OH), 8.10 m (9H, C6H5, C6H4), 9.68 s (0.4H, NH), 10.11 s
1637, 1620, 1611 (C=O) (0.6H, NH), 14.38 s (1H, OH)
272 274 3148 br (NH, OH), 1634,
1600 br (C=O)
233 235 3210 sh, 3170 (NH, OH), 8.25 m (8H, 2C6H4), 9.90 br.s (1H, NH), 14.40 br.s
1638, 1610 (C=O) (1H, OH)
220 222 3165 br (NH, OH), 1637, 8.25 m (8H, 2C6H4), 9.75 s (0.4H, NH), 9.99 s (0.6H,
1601 (C=O) NH), 14.42 s (1H, OH)
IVf
IVg
IVh
IVi
IVj
IVk
Va
3.92 s (3H, CH3O), 8.20 m (8H, 2C6H4), 9.70 br.s (0.5H,
NH), 10.35 br.s (0.5H, NH), 14.30 br.s (1H, OH)
276 277 3210 sh, 3156 br, (NH, 3.91 s (3H, CH3), 7.75 m (8H, 2C6H4), 9.87 br.s (0.4H,
OH), 1634, 1602 (C=O) 10 32 br.s. (0.6H, NH), 14.18 br.s.
56 57 1712 (COOC2H5), 1656
(C=O)
50
1.41 t (3H, CH3CH2), 3.57 s (3H, NCH3), 4.04 s (3H,
CH3O), 4.34 q (2H, CH3CH2), 7.65m (5H, C6H5)
84c
Vb
45, 79c 98 100 1712 (COOC2H5), 1654
(C=O)
Vc
48, 87c
65 67 1718 (COOC2H5), 1644
(C=O)
1.31 t (3H, CH3CH2), 2.11 s (3H, CH3N), 3.75 s (3H,
CH3OC6H4), 4.05
s (3H, CH3O), 4.30 q (2H,
CH3CH2), 7.00 q (4H, C6H4), 7.92 (2H, C6H4)
VIa
VIb
46
39
43 45 2136 (N2), 1720 br (C=O)
69 70 2132 (N2), 1718 br (C=O) 1.18 t (3H, CH3CH2), 2.15 s (3H, CH3C6H4), 3.78 s (3H,
CH3O), 4.18 q (2H, CH3CH2), 6.68 s (1H, CH), 7.15 q
(4H, C6H4), 7.55 d (2H, C6H4)
VIc
41
79 80 2146 (N2), 1712 br (C=O) 1.32 t (3H, CH3CH2), 3.88 s (3H, CH3O), 4.22 q
(2H, CH3CH2), 6.78 s (1H, CH), 7.26 d (2H, C6H4),
7.56 d (2H, C6H4)
a
Solutions of compounds IVe k, Va in DMSO-d6 CCl4, 1: 3, of compounds Vc, VIb in DMSO-d6, of compound VIc in CDCl3.
The reported yield corresponds to cyclization of the respective pentanetrione effected by triethylamine.
Yield of reaction product formed from the corresponding pyrazole and diazomethane.
b
c
1
Compounds IVa k were isolated from the reaction
1600 1611 cm . The ester carbonyl gives rise to an
mixture in amounts not exceeding 10% from the
theoretical quantity for even at the equimolar ratio of
the reagents the reaction took several routes. The
previously unknown pyrazoles IVe k were also
obtained by an independent synthesis treating diazo
compounds IIIe, i m, o with triethylamine along
procedure [4] (Table 3).
absorption band in the IR spectrum of compound IVe
at 1676 cm .
1
In the mass spectrum of pyrazole IVj unlike the
mass spectrum of initial diazopentanetrione IIIm the
molecular peak is observed with m/z 415/417 (12/10)
[M]+ and fragment ions (m/z, Irel, %): 183/185
(100/95) [BrC6H4CO]+ , 155/157 (48/42) [BrC6H4]+ ,
150 (79) [O2NC6H4CO]+ .
In the IR spectra recorded from mulls of com-
pounds IVe k in mineral oil are present broad ab-
1
According to H NMR spectra compounds IVf k
1
sorption bands or plateau at 3148 3329 cm char-
exist in solution as two tautomers. As a result the
signals of NH and OH protons in the spectrum of
compound IVi are broadened, and the protons of NH
group in the spectra of compounds IVf h, j, k appear
as two singlets.
acteristic of the NH bonds in the heterocycle and a
broadened absorption band of the hydroxy group in
1
the region 3148 3184 cm . In the spectra of com-
pounds IVh, j a single joint broad band appeared
1
respectively in the region 3148 and 3165 cm . The
1
absorption bands of carbonyl groups of the aroyl
substituents are present in the regions 1628 1638 and
The data of H NMR spectra, the shift of absorp-
tion bands of enol hydroxy and carbonyl groups in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

CHEMISTRY OF DIAZOPOLYCARBONYL COMPOUNDS: VIII.
1647
Scheme 2.
V, R = H5C2O, R = H (a), CH3 (b), CH3O (c), Cl (d), Br (e); R = C6H5, R = Br (f); R = 4-O2NC6H4, R = H
(g), CH3O (h), Cl (i), Br (j); R = 4-BrC6H4, R = CH3O (k); V, R = H (a), CH3 (b), CH3O (c); VI, R = H (a),
CH3 (b), Cl (c).
the IR spectra to the lower frequency region, and the
presence of low-frequency absorption bands of NH
group indicate that compounds IVe k exist in forms
stabilized by intramolecular hydrogen bonds whose
character and strength depend on substituents R and
R . Compounds IVa d (R = C2H5O) have a struc-
ture of ethyl 3-pyrazolecarboxylates [4], but in [4]
has been assumed an existence of a single hydrogen
bond between a carbonyl and an enol hydroxy group.
However the shift to lower frequencies in the IR
spectra of compounds IV of the absorption of both
carbonyl groups suggests that both carbonyls are
involved into hydrogen bonds with the enol hydroxyl
and NH group of the heterocycle respectively. This
assumption is supported by the chemical transform-
ations of compounds IV.
experiment where the reaction of diazoesters IIIa, b,
d was carried out with a distilled ether solution of
diazomethane. Thus we suppressed pyrazoles IVa, b,
d formation and succeeded in isolation from the reac-
tion mixture of ethyl 5-aryl-2-diazo-5-methoxy-3-
oxopentenoates VIa c in 39 46% yield (Table 3). It
should be noted that diazoesters VIa c arise in trace
amounts also in reaction of compounds IIIa, b, d
with undistilled solution of diazomethane (TLC data).
The O-methylation of diazoesters III and their
heterocyclization into pyrazoles IV are concurrent
processes: diazoesters VIa, b do not undergo cycliza-
tion into pyrazoles IVa, b under treatment with
diazomethane.
EXPERIMENTAL
Thus the reaction of diazoesters IIIa c with excess
diazomethane gave rise to 5-aroyl-1-methyl-4-meth-
oxy-3-ethoxycarbonylpyrazoles Va c. Compounds
Va c are products of exhaustive methylation of sub-
stances IVa c, and they were also prepared by direct
methylation with diazomethane of pyrazoles IVa c
(Table 3). In the IR spectra of pyrazoles Va c the
absorption bands of both carbonyls are shifted to
high-frequency region compared to the corresponding
bands in the spectra of initial compounds IVa c.
IR spectra were recorded on spectrophotometers
Specord M-80 or FSM-1201 from mulls in mineral
oil. H NMR spectra were registered on spectrometer
1
Bruker WR-80-SY (80 MHz), internal reference
HMDS, solvents CHCl3, DMSO-d6. Mass spectra
were measured on Varian MAT-311A instrument in
the following mode: emission current 1000mA, ioniz-
ing electrons energy 70 eV, vaporizer temperature
120 150 C, source temperature 200 C. The reaction
progress was monitored, purity and homogeneity of
compounds synthesized was checked by TLC on
Silufol UV-254 plates, eluent ether benzene acetone,
10: 9: 1, development in iodine vapor. The elemental
analyses are given in Table 4.
The cyclization mechanism of diazo compounds
III into pyrazole derivatives IV when treated with
diazomethane is likely to follow the same pattern as
that described in [4] for reaction of enol form A with
triethylamine. However in the former case the reac-
tion is catalyzed by trace amounts of alkali retained in
diazomethane prepared by decomposition of methyl-
nitrosourea [8]. Thus suggestion was supported by the
1,5-Diaryl-2-diazopentane-1,3,5-triones IIIi o.
A solution of 0.01 mol of 5-aryl-2,3-dihydrofuran-
2,3-dione Ia e and 0.01 mol of diazo compound II in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1648
STEPANOVA et al.
Table 4. Elemental analyses of compounds IIIi o, IVe k, V VIa c
Found, %
Calculated, %
Compd.
Formula
no.
C
H
Hlg
N
C
H
Hlg
N
IIIi
IIIj
IIIk
IIIl
IIIm
IIIn
IIIo
IVe
IVf
IVg
IVh
IVi
IVj
IVk
Va
Vb
Vc
54.91
60.62
58.71
54.80
49.14
67.83
53.97
46.19
55.18
60.59
58.75
55.0
49.13
53.99
62.58
63.69
60.29
61.40
62.37
54.39
3.11
3.20
3.69
2.79
2.32
4.70
3.38
3.16
2.16
3.17
3.49
2.79
2.31
3.31
6.99
6.05
5.79
5.08
5.70
4.42
21.58
7.62
12.33
11.48
11.46
10.01
8.21
6.91
8.38
8.19
12.30
11.32
11.38
10.00
6.81
9.90
9.09
8.71
10.12
9.59
C17H11BrN2O3
C17H11N3O5
C18H13N3O6
C17H10ClN3O5
C17H10BrN3O5
C19H16N2O4
C18H13BrN2O4
C13H11BrN2O4
C17H11BrN2O3
C17H11N3O5
55.0
60.54
58.86
54.93
49.06
67.85
53.88
46.04
55.0
60.54
58.86
54.93
49.06
53.88
62.49
63.57
60.37
61.31
62.49
54.47
2.99
3.29
3.57
2.71
2.42
4.79
3.26
3.27
2.99
3.29
3.57
2.71
2.42
3.26
7.06
6.00
5.70
5.14
5.59
4.24
21.53
7.55
12.46
11.44
11.3
10.09
8.33
6.98
8.26
7.55
12.46
11.44
11.30
10.09
6.98
9.72
9.27
8.80
10.21
9.72
9.50
19.31
9.54
19.20
19.98
23.41
21.57
19.91
23.56
21.53
C18H13N3O6
9.47
19.39
19.80
C17H10ClH3O5
C17H10BrN3O5
C18H13BrN2O4
C15H16N2O4
C16H18N2O4
C16H18N2O5
C14H14N2O4
C15H16Cl2O4
C14H13ClN2O4
9.54
19.20
19.91
VIa
VIb
VIc
11.60
9.00
11.48
9.07
40 ml of anhydrous benzene or CCl4 was heated at
reflux for 2 h. The solvent was evaporated, the
residue was recrystallized from hexane (compound
IIIi), acetonitrile (compounds IIIj m), or ethanol
(compounds IIIn, o).
Ethyl 5-aryl-2-diazo-5-methoxy-3-oxopenteno-
ates VIa c. To a solution of 0.01 mol of diazoester
IIIa or IIIb, c in 15 ml of anhydrous acetone at
5 0 C while stirring was added a solution of
0.03 mol of diazomethane in 45 ml of ether that had
been preliminary dried over KOH pellets and distil-
led. In 8 h the solvent was evaporated, and the
residue recrystallized from methanol.
5-Aroyl-4-hydroxy-3-ethoxycarbonylpyrazoles
IVa e, 3,5-diaroyl-4-hydroxypyrazoles IVf k. A
solution of 0.01 mol of diazo compound III and
0.01 mol of triethylamine in 50 ml of ethanol was
kept for 48 h at 20 25 C. The precipitate was filtered
off and recrystllized from ethanol or acetone.
REFERENCES
1. Andreichikov, Yu.S., Vyaznikova, N.G., and Za-
lesov, V.V., Zh. Org. Khim., 2002, vol. 38, p. 17.
2. Andreichikov, Yu.S., Gein, V.L., and Gein, L.F., Zh.
Org. Khim., 1978, vol. 14, p. 2234.
3. Andreichikov, Yu.S. and Kolobova, M.P., Zh. Org.
Khim., 1992, vol. 28, p. 1692.
5-Aroyl-1-methyl-4-methoxy-3-ethoxycarbonyl-
pyrazoles Va c. (a) To a solution of 0.01 mol of di-
azoester IIIa in 30 ml of chloroform at 5 0 C
while stirring was added a solution of 0.04 mol of
diazomethane in 60 ml of ether, and the mixture was
maintained for 24 h at 5 0 C. The solvent was
evaporated, the residue was recrystallized from
methanol.
4. Andreichikov, Yu.S., Gein, V.L., and Gein, L.F., Zh.
Org. Khim., 1981, vol. 17, p. 631.
5. Zalesov, V.V., Vyaznikova, N.G., and Andreichi-
kov, Yu.S., Zh. Org. Khim., 1995, vol. 31, p. 1213.
6. Zalesov, V.V., Vyaznikova, N.G., and Andreichi-
kov, Yu.S., Zh. Org. Khim., 1996, vol. 32, p. 735.
7. Aliev, Z.G., Vyaznikova, N.G., Zalesov, V.V., Kata-
ev, S.S., Andreichikov, Yu.S., and Atovmyan, L.O.,
Izv. Akad. Nauk, Ser. Khim., 1997, p. 2260.
(b) To a suspension of 0.01 mol of compound IVa
in 30 ml of toluene at 5 0 C while stirring was
added a solution of 0.03 mol of diazomethane in
45 ml of ether, and the mixture was stirred till
complete dissolution of the precipitate. The solvent
was evaporated, the residue recrystallized.
8. Organicheskie reaktsii (Organic Reactions), 1948,
vol. 1, p. 67.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003