4-aryl-2,4-dioxobutanoic acids and their derivatives in reactions with diazoalkanes

Article abstract of DOI:10.1023/A:1020343221719

By treating 4-aryl-2,4-dioxobutanoic acids or their alkyl esters with diazomethane alkyl 4-aryl-2-methoxy-4-oxo-2-butenoates and 1-R-3-aroyl-4-methoxy-4-methoxycarbonyl-4,5-dihydropyrazoles were prepared. O-Alkyl derivatives and substituted pyrazoles were

Full text of DOI:10.1023/A:1020343221719

Russian Journal of Organic Chemistry, Vol. 38, No. 6, 2002, pp. 840 844. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 6, 2002,
pp. 883 887.
Original Russian Text Copyright
2002 by Zalesov, Kataev, Pulina, Kovylyaeva.
4-Aryl-2,4-dioxobutanoic Acids and Their Derivatives
in Reactions with Diazoalkanes
V. V. Zalesov1, S. S. Kataev2, N. A. Pulina3, and N. V. Kovylyaeva4
1Perm State University, Perm, 614600 Russia
2Perm Regional Forensic Expertise Office, Perm, Russia
3Perm State Parmaceutical Academy, Perm, Russia
4Research Institute of Vaccines and Serum at the Research and Production Association Biomed , Perm, Russia
Received July 17, 2001
Abstract By treating 4-aryl-2,4-dioxobutanoic acids or their alkyl esters with diazomethane alkyl 4-aryl-2-
methoxy-4-oxo-2-butenoates and 1-R-3-aroyl-4-methoxy-4-methoxycarbonyl-4,5-dihydropyrazoles were
prepared. O-Alkyl derivatives and substituted pyrazoles were also obtained by reaction of 4-aryl-2,4-oxo-
butanoic acids aryl amides with diazomethane and diazoethane.
4-Aryl-2,4-dioxobutanoic acids, their alkyl esters
and arylamides were formerly established to exist
both in crystalline state and in solutions in an enol
form with an internal hydrogen bond (IHB) of
H-chelate type with the proton of the H-chelate ring
localized at the oxygen C2, i.e., as Z-isomers, 4-aryl-
2-hydroxy-4-oxo-(Z)-2-butenoic acids, their alkyl
esters, and amides [1 3]. An example of reaction of
diazomethane with alkyl 4-aryl-2,4-dioxobutanoates
resulting in -O-methyl derivatives of the initial
esters was described [4]. Diphenyldiazomethane with
4-aryl-2,4-dioxobutanoic acids affords benzhydryl
esters of the acids, and with alkyl esters thereof arise
products of -O-alkylation and -C-alkylation [5].
Products of 1,3-dipolar cycloaddition of diphenyldi-
azomethane to the multiple C2= C 3 bond of the esters
were mentioned in [6]. Arylamides of the acids with
diphenyldiazomethane furnished products of -C-
alkylation [7]. Since the reactivity of diazo comp-
ounds is very high, and in the carbonyl substrate exist
several reactive centers the nearly total lack of hetero-
cyclic compounds among the products suggests that
not all possible directions of reactions between 4-aryl-
2,4-dioxobutanoic acids and their derivatives with
diazo compounds are revealed.
by the other methods [8]. As testified by TLC, the
reaction was not selective, and in the reaction mixture
were present from two to three impurity compounds.
Unlike diazomethane the less reactive ethyl diazo-
acetate selectively reacted with acids Ia e furnishing
a sole product, ethoxycarbonylmethyl 4-aryl-2-hydr-
oxy-4-oxo-(Z)-2-butenoate (IIg j) (Tables 1, 2,
Scheme 1). Further reaction of acids Ia e with ethyl
diazoacetate did not occur even at heating. At the
ratio diazomethane to acid I 2: 1 the reaction gave
rise to several products, methyl 4-aryl-2-methoxy-4-
oxo-(Z)-2-butenoates (IIIa e) prevailing. From acids
Ia, c, d with diazomethane were obtained esters IIIa
c. Esters IIIa c, and also ethyl 4-aryl-2-methoxy-4-
oxo-(Z)-2-butenoates (IIId, e) were obtained by treat-
ing with diazomethane respectively esters IIa, c, e,
and ethyl 4-aryl-2-hydroxy-4-oxo-(Z)-2-butenoates
(IIk, l) at the reagents ratio 1: 1.
The IR spectra of compounds IIa l contain one
(for compounds IIa f, k, l) [3] or two (for com-
pounds IIg j) absorption bands of ester carbonyl in
1
the region 1750 1762, 1730 1735 cm . The absorp-
tion band of the ketone carbonyl C4= O involved into
the intramolecular hydrogen bond is observed at
1
1605 1610 cm . In contrast to compounds II in the
IR spectra of compounds IIIa e lacking intramole-
We established that diazomethane vigorously
reacted with 4-aryl-2-hydroxy-4-oxo-(Z)-2-butenoic
acids (I) affording a mixture of products. The com-
position of the mixture depended on the reaction con-
ditions and reagents ratio. For instance, at equimolar
amounts of acids Ia f and diazomethane the final
products were methyl 4-aryl-2-hydroxy-4-oxo-(Z)-2-
butenoates (IIa f) that had been previously obtained
cular hydrogen bond the absorption band of the C4= O
1
group shifts to higher frequencies (1640 1660 cm ),
and the ester carbonyl absorbs in the region 1712
1
1732 cm .
In the UV spectra of acids Ia f appears an absorp-
tion maximum in the longwave region at
311
328 nm (log 3.17 3.26). The position andminaxtensity
1070-4280/01/3806-840$27.00 2002 MAIK Nauka/Interperiodica

4-ARYL-2,4-DIOXOBUTANOIC ACIDS AND THEIR DERIVATIVES
841
Scheme 1.
I, II, R = H (a, g), CH3 (b), CH3O (c, h, k), Cl (d, i), Br (e, j, l), C2H5O (f); III, Alk = CH3: R = H (a), CH3O
(b), Cl (c); Alk = C2H5, R = CH3O (d), Br (e); IV, R = Cl (a), C2H5O (b).
Scheme 2.
V, R2 = H: R1 = H (a), Cl (b); R1 = H, R2 = p-Cl (c); R1 = Br, R2 = o-CH3OCO (d); VI, R1 = R2 = H: R3 = H
(a), CH3 (b); R1 = Cl, R2 = R3 = H (c); R1 = H, R2 = Cl, R3 = CH3 (d).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

842
ZALESOV et al.
Table 1. Yields, melting points, IR and 1H NMR spectra of compounds IIg j, IIIa e, IVa c, VIa d, VII IX
Compd. Yield,
1
mp,
C
IR spectrum, , cm
1H NMR spectrum, , ppm
no.
%
IIg
84
80 82 1752, 1730 (COO), 1610 (C4=O, 1.26 t (3H, CH3), 4.22 q (2H, CH2), 4.90 s (2H, CH2),
C=C)
7.15 s (1H, CH), 7.70 s (5H, C6H5), (CH3)2SO-d6
IIh
IIi
91
88
78 80 1762br (COO), 1605 (C4=O, C=C)
93 95 1750, 1730 (COO), 1605 (C4=O, 1.22 t (3H, CH3), 4.20 q (2H, CH2), 4.88 s (2H, CH2),
C=C)
7.15 s (1H, CH), 7.80 s (4H, C6H4), (CH3)2SO-d6
IIj
90
45
81
69
84
78
60
71
94 96 1755, 1735 (COO), 1610 (C4=O, 1.25 t (3H, CH3), 4.20 q (2H, CH2), 4.90 s (2H, CH2),
C=C)
7.14 s (1H, CH), 7.90 s (4H, C6H4), (CH3)2SO-d6
IIIa
IIIb
IIIc
IIId
IIIe
IVa
IVb
Oily
substance
1732 (COO), 1660 (C4=O, C=C) 3.78 s (6H, 2CH3), 6.21 s (1H, CH), 7.38 s (5H, C6H5),
CCl4
38 39 1730 (COO), 1656 (C4=O, C=C) 3.60 s (3H, CH3OC6H4), 3.74 s (6H, 2CH3), 6.75 s (1H,
CH), 7.63 q (4H, C6H4), CHCl3-d
66 67 1726 (COO), 1651 (C4=O, C=C) 3.85 s (6H, 2CH3), 6.90 s (1H, CH), 7.63 q (4H, C6H4),
CHCl3-d
46 48 1712 (COO), 1640 (C4=O, C=C) 1.38 t (3H, CH3), 3.75 s (6H, 2CH3), 4.32 q (2H, CH2),
6.05 s (1H, CH), 7.65 q (4H, C6H4), CHCl3-d
81 83 1721 (COO), 1653 (C4=O, C=C) 1.40 t (3H, CH3), 3.81 s (6H, 2CH3), 4.35 q (2H, CH2),
6.25 s (1H, CH), 7.58 q (4H, C6H4), CHCl3-d
169 171 3375 (NH), 1753 (COOCH3), 1665 3.11 s (3H, CH3O), 3.61 s (3H, CH3OCO), 3.91 s (2H,
(C4=O), 1619 (C=N)
CH2), 7.68 q (4H, C6H4), 9.83 s (1H, NH), CHCl3-d
156 157 3310 (NH), 1741 (COOCH3), 1658 1.28 t (3H, CH3), 3.11 s(3H, CH3O), 3.61 s(3H, CH3OCO),
(C4=O), 1613 (C=N)
3.88 q (2H, CH2), 4.00 d (2H, CH2), 7.35 q (4H, C6H4),
9.55 s (1H, NH), CHCl3-d
1.78 s (3H, CH3N), 3.15 s (3H, CH3O), 3.55 s (3H,
CH3OCO), 3.75 s (3H, CH3OC6H4), 4.01 d (2H, CH2),
7.51 q (4H, C6H4), (CH3)2SO-d6
IVc
65
176 177 1735 (COOCH3), 1660 (C4=O),
1610 (C=N)
VIa
VIb
VIc
VId
VII
VIII
IX
38
18
15
27
41
51
48
146 147 3320 (NH), 1698 (CONH), 1660 3.68 s (3H, CH3O), 5.98 s (1H, CH), 7.25 s (11H,
(C4=O)
2C6H5+NH), (CH3)2SO-d6
86 88 3300 (NH), 1685 (CONH), 1670 1.28 t (3H, CH3), 3.45 q (2H, CH2), 7.38 s (11H,
(C4=O)
2C6H5+CH), 9.15 s (1H, NH), CHCl3-d
80 83 3336 (NH), 1684 (CONH), 1664
(C4=O)
76 78 3311 (NH), 1685 (CONH), 1675
(C4=O)
205 207 3315 (NH), 1660 br (C=O), 1615 6.30 s (1H, CH), 7.26 s (9H, C6H5+ C 6H4), 10.78 s
(decomp.) (C=N, C=C)
216 218 3308 (NH), 1692, 1684 (C=O),
1628, 1616 (C=N, C=C)
(1H, NHCO), 12.13 s (1H, NH), (CH3)2SO-d6
3.93 s (3H, CH3), 7.60 s (10H, C6H5+ C 6H4+CH),
10.91 s (1H, NH), (CH3)2SO-d6
181 183 3204 br (NH), 1708 (COOCH3),
3.82 s (3H, CH3O), 3.95 s (3H, CH3N), 6.75 s (1H, CH),
1692, 1674 (C=O), 1603 (C=N, 7.58 s (8H, 2C6H4), 12.12 s (1H, NH), (CH3)2SO-d6
C=C)
of the maximum are retained on going to methyl
esters IIa f : max 313 339 nm (log 3.15 3.40), and
instance, on treating acids Id, f with excess diazo-
methane 3-aroyl-4-methoxy-4-methoxycarbonyl-4,5-
dihydropyrazoles (IVa, b) were obtained, and with
acid Ic the diazomethane afforded 1-methyl-4-meth-
oxy-3-(4-methoxybenzoyl)-4-methoxycarbonyl-4,5-di-
hydropyrazole (IVc). The latter product resulted from
N-methylation of the intermediately arising 4-meth-
also to ethoxycarbonylmethyl esters IIg j:
316
max
338 nm (log 4.18 4.24).
Compounds IIIa e were obtained in 45 84%
yield, but the yields notably decreased in reactions of
acids I or esters II with excess diazomethane. For
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

4-ARYL-2,4-DIOXOBUTANOIC ACIDS AND THEIR DERIVATIVES
843
Table 2. Elemental analyses of compounds IIg j, IIIa e, IVa c, VIa d, VII IX
Found, %
Calculated, %
Compd.
no.
Formula
C
H
Hlg
N
C
H
Hlg
N
IIg
IIh
IIi
IIj
60.46
58.50
53.69
46.92
65.56
62.37
56.58
63.71
49.94
52.77
58.96
58.89
72.75
73.32
64.55
65.43
62.76
63.75
54.14
5.03
5.21
4.13
3.60
5.40
5.68
4.19
6.03
4.03
4.32
5.84
5.88
5.24
5.71
4.34
4.85
3.58
4.02
3.54
C14H14O6
C15H16O7
C17H13ClO3
C17H13BrO3
C12H12O4
C13H14O5
C12H11ClO4
C14H16O5
C13H13BrO4
C13H13ClN2O4
C15H18N2O5
C15H18N2O5
C17H15NO3
C18H17NO3
C17H14ClNO3
C18H16ClNO3
C17H12ClN3O2
C18H14ClN3O2
C20H16BrN3O4
60.43
58.44
53.77
47.08
65.45
62.39
56.60
63.63
49.86
52.62
58.82
58.82
72.58
73.20
64.67
65.56
62.68
63.63
54.31
5.07
5.23
4.19
3.67
5.49
5.64
4.35
6.10
4.18
4.42
5.92
5.92
5.37
5.80
4.47
4.89
3.71
4.15
3.65
11.41
22.51
11.34
22.37
IIIa
IIIb
IIIc
IIId
IIIe
IVa
IVb
IVc
VIa
VIb
VIc
VId
VII
VIII
IX
14.07
13.92
25.64
12.22
25.52
11.95
9.32
9.03
9.07
4.76
4.82
4.34
4.07
12.73
12.14
9.37
9.44
9.15
9.15
4.98
4.74
4.44
4.25
12.90
12.37
9.50
11.39
10.97
11.06
10.52
18.31
11.23
10.75
10.88
10.43
18.07
oxy-3-(4-methoxybenzoyl)-4-methoxycarbonyl-4,5-di-
hydropyrazole that we failed to isolate under the
reaction conditions used. All pyrazole derivatives
obtained are products of 1,3-dipolar cycloaddition of
diazomethane across the C2= C 3 bond with obligatory
attack of the nucleophilic carbon atom of diazo-
methane on C2 atom of substrate. No isomeric pro-
ducts of the obtained 4-aroyl-5-methoxy-5-methoxy-
carbonyl-4,5-dihydropyrazoles were detected. Note
that with excess diazomethane arose complicated
mixtures of products (up to 6 substances as showed
TLC) that we often were unable to separate.
azole (IX). Pyrazoles VII IX arise apparently from
methanol elimination during workup from primary
products, 4-methoxy-4,5-dihydropyrazole derivatives.
EXPERIMENTAL
IR spectra were recorded on spectrometers UR-20
1
or Specord M80 from mulls in mineral oil. H NMR
spectra were registered on instruments RYa-2310
(60 MHz) and Bruker WR-80-SY (80 MHz), internal
reference HMDS, as solvents were used CDCl3 and
DMSO-d . UV spectra were taken on SF-46 device
6
4
from solutions in ethanol of 10 M concentration.
The reaction progress was monitored and the homo-
geneity of compounds obtained was checked by TLC
on Silufol UV-254 plates in the solvents system
ether benzene acetone (10: 9: 1).
Similarly to acids I and esters II reacted with
diazoalkanes also 4-aryl-2-hydroxy-4-oxo-(Z)-2-
butenoic acids arylamides (V). For instance,
among the products obtained from arylamides Va c
and diazomethane and diazoethane at the equimolar
amounts of reagents were 2-alkoxy-4-aryl-4-oxo-2-
butenoic acids aryl amides (VIa d) (Tables 1, 2,
Scheme 2).
Ethoxycarbonylmethyl 4-aryl-2-hydroxy-4-oxo-
Z-2-butenoates (IIg j). A mixture of 0.01 mol of
acid Ia e and 0.011 mol of ethyl diazoacetate in
20 ml of ethanol was boiled for 2 h. The reaction
mixture was then maintained for 3 h at 5 0 C. The
precipitate was filtered off and recrystallized from
ethanol.
At excess diazomethane amides Vb d gave a mix-
ture of compounds from which were isolated respec-
tively
4-phenylcarbamoyl-3-(4-chlorobenzoyl)pyr-
azole (VII), 3-benzoyl-1-methyl-4-(4-chlorophenyl-
carbamoyl)pyrazole (VIII), and 3-(4-bromobenzoyl)-
1-methyl-4-(2-methoxycarbonylphenylcarbamoyl)pyr-
Alkyl 4-aryl-2-methoxy-4-oxo-Z-2-butenoates
(IIIa e). To a solution of 0.01 mol of ester
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

844
ZALESOV et al.
IIa, c, e, k, l in 30 ml of chloroform at 5 0 C was
added while stirring a solution of 0.01 mol of diazo-
methane in 15 ml of ether. After standing for 24 h
the solution was evaporated, the residue was re-
crystallized from hexane.
ether. After standing for 24 h the solution was
evaporated, the residue was recrystallized from
chloroform (compound VII), acetone (compound
VIII), or ethanol (compound IX).
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1-R-3-Aroyl-4-methoxy-4-methoxycarbonyl-4,5-
dihydropyrazoles (IVa c). To a solution of 0.01 mol
of compound Ic, d, f in 30 ml of chloroform was
added at stirring a solution of 0.06 mol of diazo-
methane in 90 ml of ether. After standing for 24 h the
solution was evaporated, the residue was recrystalliz-
ed from toluene (compounds IVa, b) or ethanol (com-
pound IVc).
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2-Alkoxy-4-aryl-4-oxo-2-butenoic acids aryl-
amides VIa d. To a solution of 0.01 mol of com-
pound Va c in 50 ml of dioxane at 5 10 C while
stirring was added 0.01 mol of diazomethane (diazo-
ethane) in 15 ml of ether. After standing for 24 h the
solution was evaporated, the residue was recrystalliz-
ed from tetrachloromethane (compound VIa) or
hexane.
4-Phenylcarbamoyl-3-(4-chlorobenzoyl)pyrazole
(VII), 3-benzoyl-1-methyl-4-(4-chlorophenylcarb-
amoyl)pyrazole (VIII), and 3-(4-bromobenzoyl)-1-
methyl-4-(2-methoxycarbonylphenylcarbamoyl)pyr-
azole (IX). To a solution of 0.01 mol of compound
Vb d in 40 ml of dioxane at 5 10 C while stirring
was added 0.04 mol of diazomethane in 60 ml of
8. Khimiya
pyatichlennykh
2,3-dioxogeterotsiklov
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002