Synthesis of tricarbonylmethane derivatives of pyridines, pyrimidines, pyridazines, and pyrazoles by anionic ortho-Fries rearrangement

Article abstract of DOI:10.1007/pl00013495

Heterocyclic 1,3-dicarbonyl systems, such as 4-hydroxy-2-pyridones, 6-hydroxy-4-pyrimidones, and 5-hydroxy-1-phenyl-3-pyrazolones, are converted with a number of aromatic acid chlorides to their enol esters which can be rearranged in the presence of KCN, triethylamine, and 18-crown-6 as catalyst to yield heterocyclic aryl ketones. This reaction can also be performed in a one-pot procedure without isolation of the esters. Aryl esters of 5-hydroxy-3-pyridazinone can be prepared in the same manner, but not be rearranged.

Full text of DOI:10.1007/pl00013495

Monatshefte fuÈr Chemie 129, 871±885 (1998)
Synthesis of Tricarbonylmethane Derivatives
of Pyridines, Pyrimidines, Pyridazines,
and Pyrazoles by Anionic ortho-Fries
Rearrangement
Ã;a
Barbara Schnell and Thomas Kappe
Institute of Organic Chemistry, Karl Franzens University Graz, A-8010 Graz, Austria
Summary. Heterocyclic 1,3-dicarbonyl systems, such as 4-hydroxy-2-pyridones, 6-hydroxy-4-
pyrimidones, and 5-hydroxy-1-phenyl-3-pyrazolones, are converted with a number of aromatic acid
chlorides to their enol esters which can be rearranged in the presence of KCN, triethylamine, and 18-
crown-6 as catalyst to yield heterocyclic aryl ketones. This reaction can also be performed in a one-
pot procedure without isolation of the esters. Aryl esters of 5-hydroxy-3-pyridazinone can be
prepared in the same manner, but not be rearranged.
Keywords. Anionic ortho-Fries rearrangement; 4-Hydroxy-2(1H)-pyridones; 6-Hydroxy-4(3H)-
pyrimidones; 5-Hydroxy-3(2H)-pyridazinones; Pyrazolidine-3,5-diones.
Synthese von Tricarbonylmethanderivaten des Pyridins, Pyrimidins und Pyrazols durch
anionische ortho-Fries Umlagerung
Zusammenfassung. Heterocyclische 1,3-Dicarbonylsysteme (``Malonylheterocyclen'') wie 4-
Hydroxy-2-pyridone, 6-Hydroxy-4-pyrimidone und 5-Hydroxy-3-pyrazolone (``Pyrazolin-3,5-
È
È
È
dione'') werden mit aromatischen Saurechloriden in ihre Enolester ubergefuhrt, welche mit Hilfe
von KCN, Triethylamin und 18-Crown-6 als Katalysator in Arylketone umgelagert werden. Diese
Reaktion kann auch als Eintopfverfahren ohne Isolierung der Ester durchgefuÈhrt werden. Arylester
È
des 5-Hydroxy-3-pyridazinones konnen auf die gleiche Art hergestellt, aber nicht umgelagert
werden.
Introduction
The 4-hydroxy-2(1H)-pyridone system is noteworthy for several reasons. The
fundamental structure can be found in many natural products, such as ¯avipucin
[1], the long known and highly toxic ricinine [2, 3], and the yellow pigments
bassianin [4] and tenellin [5]. The latter two compounds have a 3-acyl-4-hydroxy-
Ã
Corresponding author
Dedicated to Prof. Gottfried Heinisch on the occasion of his 60th birthday
a

872
B. Schnell and T. Kappe
2-pyridone skeleton, a structural moiety which is common for a large number of
antibiotic substances such as ilicicolin H [6], funiculosin [7], harzianopyridon [8],
sambutoxin [9], mocimycin [10], and aurodox [10], produced by a variety of
Streptomyces species. Moreover, substances with this structure belong to the large
group of so-called ``cyclic tricarbonylmethane compounds'' which play an impor-
tant role in agricultural chemistry, whether they are carbocyclic or heterocyclic,
oximated or not [11, 12].
In recent years we have developed an easy entrance to the ®eld of aliphatic 3-
acyl derivatives in this series of heterocycles by ring opening of pyrono derivatives
[13±15]. However, aroyl derivatives of this type are not accessible by this route.
Therefore, we have tried the classical and the anionic Fries rearrangement with 4-
aroyloxy-2-quinolones and coumarins [12, 16]. We have now extended this
procedure to obtain heterocyclic tricarbonylmethane compounds with potential
herbicidal activity by introducing the appropriate aroyl substituents into 4-
hydroxy-2(1H)-pyridones (1), 6-hydroxy-4(3H)-pyrimidones (8), 5-hydroxy-
3(2H)-pyridazinones (11), and pyrazolidine-3,5-diones (17).
Results and Discussion
The starting ``malonyl heterocycles'' 1, 8, 11, and 17 represent enolized heterocyclic
1,3-dicarbonyl systems and can be converted conveniently to their arylesters (3a±l,
9a±m, 12a±c, and 18a±e), by two methods. With method A, two equivalents of the
acid chlorides 2 are reacted with the educts in sodium carbonate solution. However,
under these conditions the acid chlorides are partially hydrolyzed. Since some of
them are expensive, the preferred mode of preparation uses only a small excess
(20%) of 2 in dry toluene with one equivalent of triethylamine as base (Method B).
This method is also advantageous since it allows to perform a one-pot reaction
sequence from the starting substances 1, 8, and 17 directly to the rearranged
ketones 4, 10, and 16 as shown in the next paragraph.
As noted before, the Lewis acid catalyzed Fries rearrangement of aromatic
esters of malonyl heterocycles works only with the unsubstituted benzoyl ester
[12]. Fries rearrangement reactions catalyzed with 4-dimethylaminopyridine [17]
or cyanide (in the form of acetone cyanohydrine) in the presence of triethylamine
in acetonitrile have been described for 1,3-cyclohexanedione derivatives [18].
Experiments with substrates 3, 9, 12, and 18 under these conditions were unsuc-
cessful. However, the use of KCN (2 equivalents), triethylamine (1 equivalent),
and a catalytic amount of 18-crown-6 in toluene gave the rearranged compounds
in good yields. The use of acetonitrile as solvent lead to a number of side
products. The mechanism of this variety of the Fries rearrangement is not yet
resolved. It may be assumed that under the reaction conditions small amounts of
aroylonitriles and the anions of the heterocycles are generated and that these two
intermediates give the thermodynamically more stable C-acylated compounds.
As already mentioned, the mode of the ester preparation using 2 and
triethylamine in toluene allows a one-pot preparation of the rearranged
products 4 and 10 if KCN and 18-crown-6 as catalysts are added after
completion of the esteri®cation. Most of the ketones were prepared by this direct
method (A).

Tricarbonylmethane Derivatives of N-Containing Heterocycles
873
Scheme 1
Aliphatic ketones of type 4 are easily converted to their oximes or oxime ethers
[19]. In view of the potential herbicidal activity of such derivatives we have
prepared the oximes 6a±c, but obtained a mixture of isomers (E/Z isomers and
oxim-enol/hydroxyaminomethylene ketone tautomers [20] are possible). There-
fore, we have converted these mixtures directly by thermal Beckmann rearrange-
ment [19] to the oxazolo[4,5-c]pyridones 7a±c. The three component reaction of 1
with triethyl orthoformiate and aniline lead to the phenylaminomethylene-
pyridine-dione 5.
The 5-hydroxy-3-pyridazinone 11 was readily converted to the ester 12 with 2
and triethylamine in toluene; however, all attempts to rearrange these derivatives to
the ketones 13 failed (Scheme 3). The 5-hydroxy-3-chloro-pyridazine 14 could
also be reacted by this method to its esters 15a±c. The attempted Fries
rearrangement of 15a under standard conditions with KCN led to the phenyl
ketone 16 in which the chloro atom was exchanged against the cyano group; the
yield of 16 was, however, 20% only (Scheme 3).

874
B. Schnell and T. Kappe
Scheme 2
Scheme 3
The 5-membered hydroxypyrazolone 17 (usually described as 1-phenyl-pyrazoli-
din-3,5-dione) leads to the formation of the O- and N-acylated compounds 18a±e
with 2 equivalents of 2 according to Method B (Scheme 4). The anionic Fries
rearrangement was successfully tested with two derivatives to afford 19a and 19b
(55% and 89% yield, respectively).

Tricarbonylmethane Derivatives of N-Containing Heterocycles
875
Scheme 4
Experimental
Melting points were obtained on a Gallenkamp melting point apparatus, Mod. MFB-595 (open
1
capillary tubes). IR spectra were recorded on a Perkin-Elmer 298 spectrometer; (KBr-pellets). H
NMR spectra were recorded on a Varian Gemini 200 instrument (TMS as internal standard, ꢀ values
in ppm, DMSO-d6 as solvent). Elemental analyses were performed on a C,H,N-Automat Carlo Erba
1106; they agreed with the calculated values (Æ0.4%).
General procedure for the synthesis of 4-benzoyloxy-1,6-dimethyl-2(1H)-pyridones 3a±l,
6-benzoyloxy-2,3-diphenyl-4(3H)-pyrimidones 9a±m, benzoyloxy-2-methyl-6-phenyl-
3(2H)-pyridazones 12a±c, and 5-benzoyloxy-3-chloro-6-phenyl-pyridazines 15a±c
Method A
6-Hydroxy-2,3-diphenyl-4(3H)-pyrimidone (8) [21] (10 mmol) and the corresponding acid chloride
2 (20 mmol) were stirred for 24 h in aqueous sodium carbonate solution (16 g Na2CO3 Á 10 H2O in
40 ml water). The product was ®ltered by suction, washed with water, and dried.
Method B
To a solution of 4-hydroxy-1,6-dimethyl-2(1H)-pyridone (1) [22] or 8 (10 mmol) in 50 ml of dry
toluene the corresponding acid chloride 2 (12 mmol) and Et3N (10 mmol) were added. The solution
was heated for 5 h under re¯ux. After cooling to room temperature, 60 ml of CH2Cl2 were added, and
the mixture was washed several times with dilute HCl in a separatory funnel. The organic phase was
dried over Na2SO4, and the solvent was removed by evaporation.
4-Benzoyloxy-1,6-dimethyl-2(1H)-pyridone (3a; C14H13NO3)
Prepared by method B in 72% yield; m.p.: 115±118ꢀC (toluene); IR: ꢁ ˆ 3600±3280 wb, 3080 w,
1
1745 s, 1650 s, 1580 s, 1560 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 3.42 (s,
3H, NCH3), 6.23 (s, 2H, 3-H, 5-H), 7.55±7.80 (m, 3H, phenyl-H), 8.08 (dd, J ˆ 7 and 1.5 Hz, 2H,
phenyl 2-H, 6-H) ppm.

876
B. Schnell and T. Kappe
4-(4-Chlorobenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3b; C14H12ClNO3)
Prepared by method B in 82% yield; m.p.: 145±148ꢀC (1-butanol); IR: ꢁ ˆ 3080 w, 1740 s, 1660±
1
1645 s, 1590 s, 1565 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 3.48 (s, 3H,
NCH3), 6.28 (s, 2H, 3-H, 5-H), 7.70 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 8.12 (d, J ˆ 8 Hz, 2H, phenyl
2-H, 6-H) ppm.
4-(2-Chlorobenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3c; C14H12ClNO3)
Prepared by method B in 52% yield; m.p.: 105±109ꢀC (ethanol); IR: ꢁ ˆ 3580±3320 wb, 1760 s,
1650 s, 1570 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.41 (s, 3H, CH3), 3.44 (s, 3H, NCH3), 6.28
(s, 2H, 3-H, 5-H), 7.50±7.60 (m, 1H, aryl-H), 7.65±7.70 (m, 2H, aryl-H), 8.05 (dd, J ˆ 7 and 1.5 Hz,
1H, phenyl 6-H) ppm.
4-(2-Bromobenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3d; C14H12BrNO3)
Prepared by method B in 59% yield; m.p.: 104±106ꢀC (toluene).
4-(4-Chloro-2-nitrobenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3e; C14H11ClN2O5)
Prepared by method B in 56% yield; m.p.: 138±141ꢀC (ethanol).
4-(4-Methylbenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3f; C15H15NO3)
Prepared by method B in 89% yield; m.p.: 138±140ꢀC (1-butanol); IR: ꢁ ˆ 3080±2850 wb, 1740 s,
1650 s, 1595 s, 1565 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 2.42 (s, 3H, CH3),
3.45 (s, 3H, NCH3), 6.24 (s, 2H, 3-H, 5-H), 7.42 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 8.00 (d,
J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
4-(4-Methoxybenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3g; C15H15NO4)
Prepared by method B in 76% yield; m.p.: 161±164ꢀC (ethanol); IR: ꢁ ˆ 3080±2840 wb, 1725 s,
1655 s, 1605 s, 1580 m, 1560 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.39 (s, 3H, CH3), 3.43 (s,
3H, NCH3), 3.89 (s, 3H, OCH3), 6.21 (s, 2H, 3-H, 5-H), 7.10 (d, J ˆ 7 Hz, 2H, phenyl 3-H, 5-H),
8.02 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
4-(2,4-Dichlorobenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3h; C14H11Cl2NO3)
Prepared by method B in 83% yield; m.p.: 127±131ꢀC (ethanol); IR: ꢁ ˆ 3100±2850 wb, 1742 m,
1718 m, 1665 s, 1585 m, 1555 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 3.45 (s,
3H, NCH3), 6.45 (s, 2H, 3-H, 5-H), 7.65 (dd, J ˆ 7 and 1.5 Hz, 1H, phenyl 5-H), 7.88 (d, J ˆ 1.5 Hz,
1H, phenyl 3-H), 8.10 (d, J ˆ 8 Hz, 1H, phenyl 6-H) ppm.
4-(2,3-Dichloro-4-methylsulfonylbenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3i; C15H13Cl2NO5S)
Prepared by method B in 51% yield; m.p.: 150±154ꢀC (1-butanol).
4-(2-Methylbenzoyloxy)-1,6-dimethyl-2(1H)-pyridone (3j; C15H15NO3)
Prepared by method B in 60% yield; m.p.: 89±92ꢀC (ethanol); IR: ꢁ ˆ 3080±2840 w, 1740 s, 1640 s,
1595 m, 1560 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.42 (s, 3H, CH3), 2.62 (s, 3H, CH3), 3.48

Tricarbonylmethane Derivatives of N-Containing Heterocycles
877
(s, 3H, NCH3), 6.28 (d, J ˆ 2 Hz, 2H, 3-H, 5-H), 7.28±7.68 (m, 3H, phenyl H), 8.05 (dd, J ˆ 7 and
1.5 Hz, 1H, phenyl 6-H) ppm.
4-(2-Methyl-3-methoxy-4-methylsulfonylbenzoyloxy)-1,6-dimethyl-2(1H)-pyridone
(3k; C17H19NO6S)
Prepared by method B in 66% yield; m.p.: 185±187ꢀC (ethanol); IR: ꢁ ˆ 3100±2820 w, 1735 s,
1
1650 s, 1585 w, 1560 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.42 (s, 3H, CH3), 2.53 (s, 3H,
phenyl-CH3), 3.38 (s, 3H, SO2CH3), 3.48 (s, 3H, NCH3), 3.92 (s, 3H, OCH3), 6.30 (s, 2H, 3-H, 5-H),
7.85 (d, J ˆ 8 Hz, 1H, phenyl 5-H), 7.98 (d, J ˆ 8 Hz, 1H, phenyl 6-H) ppm.
4-(2-Thienylcarbonyloxy)-1,6-dimethyl-2(1H)-pyridone (3l; C12H11NO3S)
Prepared by method B in 64% yield; m.p.: 118±120ꢀC (toluene); IR: ꢁ ˆ 3110±2910 w, 1720 s,
1
1665 s, 1590 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.38 (s, 3H, CH3), 3.42 (s, 3H, NCH3),
6.22 (s, 2H, 3-H, 5-H), 7.27±7.33 (m, 1H, thiophene 4-H), 8.00 (dd, J ˆ 6 and 1.5 Hz, 1H, thiophene
3-H), 8.11 (dd, J ˆ 6 and 1.5 Hz, 1H, thiophene 5-H) ppm.
General procedure for the synthesis of 3-benzoyl-4-hydroxy-1,6-dimethyl-2(1H)-pyridones 4a±j
and 5-benzoyl-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidones 10a±i
Method A
To a solution of 1 or 8 (10 mmol) in 50 ml of dry toluene the corresponding acid chloride 2
(12 mmol) and Et3N (10 mmol) were added. The solution was heated for 5 h under re¯ux. After
cooling to room temperature, 1.36 g KCN (20 mmol), 1.4 ml Et3N (10 mmol), and catalytic amounts
(0.4±0.5 g) of 18-crown-6 were added. The reaction mixture was stirred for 72 h at room
temperature. At the end of the reaction, 60 ml of CH2Cl2 were added, and the mixture was washed
several times with dilute HCl in a separatory funnel. The organic phase was dried over Na2SO4, and
the solvent was removed by evaporation.
Method B
A mixture of 10 mmol 3a±l or 9a±m, 1.4 ml Et3N (10 mmol), 1.36 g KCN (20 mmol), and catalytic
amounts (0.4±0.5 g) of 18-crown-6 in 60 ml of dry toluene was stirred for 48 h at room temperature.
After addition of 70 ml CH2Cl2 the reaction mixture was washed several times with dilute HCl in a
separatory funnel. The organic phase was dried over Na2SO4, and the solvent was removed by
evaporation.
3-Benzoyl-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4a; C14H13NO3)
Prepared by method A in 31% yield; m.p.: 152±155ꢀC (ethanol); IR: ꢁ ˆ 3100±2840 wb, 1640±
1
1610 s, 1555 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.36 (s, 3H, CH3), 3.32 (s, 3H, NCH3),
5.97 (s, 1H, 5-H), 7.40±7.52 (m, 3H, aryl-H), 7.60 (dd, J ˆ 7 and 1.5 Hz, 2H, aryl-H), 11.45 (s, 1H,
OH) ppm.
3-(4-Chlorobenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4b; C14H12ClNO3)
Prepared by method A in 63% and by method B in 57% yield; m.p.: 152±154ꢀC (toluene); IR:
ꢁ ˆ 1650 s, 1630 s, 1560 m, 1485 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.38 (s, 3H, CH3), 3.41

878
B. Schnell and T. Kappe
(s, 3H, NCH3), 6.00 (s, 1H, 5-H), 7.54 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.72 (d, J ˆ 8 Hz, 2H,
phenyl 2-H, 6-H) ppm.
3-(2-Chlorobenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4c; C14H12ClNO3)
Prepared by method A in 62% yield; m.p.: 150±153ꢀC (1-butanol); IR: ꢁ ˆ 3200±2840 w, 1640 s,
1
1620 s, 1550 m cmꢁ1, H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 3.25 (s, 3H, NCH3),
6.10 (s, 1H, 5-H), 7.25±7.46 (m, 4H, aryl-H) ppm.
3-(2-Bromobenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4d; C14H12BrNO3)
Prepared by method A in 54% yield; m.p.: 127±130ꢀC (1-butanol); IR: ꢁ ˆ 3120±2840 wb,
1645 s, 1615 s, 1590 m, 1565 s cmꢁ1 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3),
;
3.22 (s, 3H, NCH3), 6.10 (s, 1H, 5-H), 7.20±7.45 (m, 3H, aryl-H), 7.60 (dd, J ˆ 7 and 1.5 Hz, 1H,
aryl-H) ppm.
3-(4-Methylbenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4e; C15H15NO3)
Prepared by method A in 60% yield; m.p.: 187±190ꢀC (ethanol); IR: ꢁ ˆ 3360±2800 mb, 1660 s,
1605 m, 1590 m, 1555 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.37 (s, 6H, 2ÂCH3), 3.35 (s, 3H,
NCH3), 5.97 (s, 1H, 5-H), 7.28 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.62 (d, J ˆ 8 Hz, 2H, phenyl 2-H,
6-H), 11.28 (s, 1H, OH) ppm.
3-(4-Methoxybenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4f; C15H15NO4)
Prepared by method A in 41% and method B 52% yield; m.p.: 194±197ꢀC (ethanol); IR: ꢁ ˆ 2980±
2800 w, 1665 s, 1600 s, 1545 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.32 (s, 3H, CH3), 3.35 (s,
3H, NCH3), 3.83 (s, 3H, OCH3), 5.95 (s, 1H, 5-H), 7.00 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.71 (d,
J ˆ 8 Hz, 2H, phenyl 2-H, 6-H), 11.11 (s, 1H, OH) ppm.
3-(2,4-Dichlorobenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4g; C14H11Cl2NO3)
Prepared by method A in 59% yield; m.p.: 161±164ꢀC (1-butanol); IR: ꢁ ˆ 3100±2920 w, 1665 s,
1610 s, 1560 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 3.33 (s, 3H, NCH3), 6.12
(s, 1H, 5-H), 7.32 (d, J ˆ 8 Hz, 1H, aryl-H), 7.48 (dd, J ˆ 8 and 2 Hz, 1H, aryl-H), ppm.
3-(2,3-Dichloro-4-methylsulfonylbenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone
(4h; C15H13Cl2NO5S)
Prepared by method A in 64% yield; m.p.: 195±197ꢀC (ethanol); IR: ꢁ ˆ 3140±2900 w, 1650 s,
1
1600 s, 1565 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.46 (s, 3H, CH3), 3.30 (s, 3H, SO2CH3),
3.54 (s, 3H, NCH3), 6.28 (s, 1H, 5-H), 7.62 (d, J ˆ 7 Hz, 1H, phenyl 5-H), 8.15 (d, J ˆ 7 Hz, 1H,
phenyl 6-H), 14.00 (s, 1H, OH) ppm.
3-(2-Methylbenzoyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4i; C15H15NO3)
Prepared by method A in 43% yield; m.p.: 135±137ꢀC (1-butanol); IR: ꢁ ˆ 2960±2850 w, 1640 s,
1612 s, 1555 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.22 (s, 3H, CH3), 2.38 (s, 3H, CH3), 3.28
(s, 3H, NCH3), 6.08 (s, 1H, 5-H), 7.12±7.37 (m, 4H, aryl-H) ppm.

Tricarbonylmethane Derivatives of N-Containing Heterocycles
879
3-(2-Thienylcarbonyl)-4-hydroxy-1,6-dimethyl-2(1H)-pyridone (4j; C12H11NO3S)
Prepared by method A in 53% yield; m.p.: 152±154ꢀC (1-butanol); IR: ꢁ ˆ 3090 w, 1665 s, 1585 s,
1545 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.34 (s, 3H, CH3), 3.32 (s, 3H, NCH3), 5.94 (s, 1H,
5-H), 7.16 (t, J ˆ 5 Hz, thiophene 4-H), 7.56 (dd, J ˆ 6 and 1.5 Hz, thiophene 3-H), 7.95 (dd, J ˆ 6
and 1.5 Hz, 1H, thiophene 5-H), 11.09 (s, 1H, OH) ppm.
1,6-Dimethyl-3-phenylaminomethylene-pyridine-2,4(1H,3H)-dione (5; C14H14N2O2)
A mixture of 2.8 g 1 (20 mmol) with 2.96 g triethyl orthoformiate (20 mmol) and 1.86 g aniline
(20 mmol) in 20 ml ethylene glycole was heated under stirring until the formation of ethanol started.
The temperature was increased during 20 minutes to 180ꢀC until the formation of ethanol stopped.
The reaction mixture was cooled to room temperature and treated with ethanol.
Yield: 2.30 g (48%); m.p.: 175±178ꢀC (ethanol); IR: ꢁ ˆ 3100±2800 w, 1650 s, 1615 s, 1585 s,
1550 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.25 (s, 3H, CH3), 3.30 (s, 3H, NCH3), 5.62 (s, 1H,
5-H), 7.22±7.58 (m, 5H, aryl H), 8.65±8.85 (m, 1H, NH) ppm.
2-(4-Chlorophenyl)-5,6-dimethyl-oxazolo[4,5-c]pyridin-4(5H)-one (7a; C14H11ClN2O2)
A solution of 2.78 g 4b, 1.39 g NH2OH Á HCl (20 mmol), and 1.68 g NaHCO3 (20 mmol) in 100 ml
ethanol/water (3:1) was heated for 30 minutes under re¯ux. Then the reaction mixture was poured
into ice/water, and the precipitate obtained was ®ltered after standing for 2±3 h. The crude product 6a
was dried overnight and heated next day in 30 ml ethylene glycole for 30 min under re¯ux. After
cooling the product precipitated.
Yield: 1.80 g (33%); m.p.: 262±267ꢀC (ethanol); IR: ꢁ ˆ 3100 w, 2970±2820 w, 1690 s,
1
1575 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.50 (s, 3H, CH3), 3.52 (s, 3H, NCH3), 6.80 (s,
1H, 7-H), 7.63 (d, J ˆ 7 Hz, 2H, phenyl 3-H, 5-H), 8.06 (d, J ˆ 7 Hz, 2H, phenyl 2-H, 6-H) ppm.
5,6-Dimethyl-2-(4-methylphenyl)oxazolo[4,5-c]pyridin-4(5H)-one (7b; C15H14N2O2)
From 2.57 g 4e (10 mmol) according to the preparation of 7a.
Yield: 1.13 g (44%); m.p.: 250±253ꢀC (ethanol); IR: ꢁ ˆ 2940±2840 w, 1675 s, 1610 w, 1588 m,
1
1565 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.40 (s, 3H, CH3), 2.50 (s, 3H, CH3), 3.54 (s, 3H,
NCH3), 6.82 (s, 1H, 7-H), 7.40 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.99 (d, J ˆ 8 Hz, 2H, phenyl 2-H,
6-H) ppm.
5,6-Dimethyl-2-(4-methoxyphenyl)-oxazolo[4,5-c]pyridin-4(5H)-one (7c; C15H14N2O3)
From 2.73 g 4f (10 mmol) according to the preparation of 7a.
Yield: 0.95 g (35%); m.p.: 235±239ꢀC (ethanol); IR: ꢁ ˆ 3060 w, 3000 ±2840 w, 1675 s, 1610 m,
1575 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.50 (s, 3H, CH3), 3.53 (s, 3H, NCH3), 3.87 (s, 3H,
OCH3), 6.81 (s, 1H, 7-H), 7.15 (d, J ˆ 10 Hz, 2H, phenyl 3-H, 5-H), 8.03 (d, J ˆ 10 Hz, 2H, phenyl
2-H, 6-H) ppm.
6-Benzoyloxy-2,3-diphenyl-4(3H)-pyrimidone (9a; C23H16N2O3)
Prepared by method A in 70% and by method B in 57% yield; m.p.: 196±198ꢀC (ethanol); IR:
ꢁ ˆ 3060 w, 1750 s, 1685 s, 1590 m, 1530 s cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 6.69 (s, 1H, 3-
H), 7.19±7.42 (m, 10H, aryl-H), 7.62±7.86 (m, 3H, aryl-H), 8.16 (dd, J ˆ 7 and 1.5 Hz, 2H, aryl-H)
ppm.

880
B. Schnell and T. Kappe
6-(4-Chlorobenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9b; C23H15ClN2O3)
Prepared by method A in 67% and by method B in 53% yield; m.p.: 147±149ꢀC (ethanol); IR:
1
ꢁ ˆ 3100±3050 w, 1790 m, 1750 s, 1690 s, 1595 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.58 (s,
1H, 3-H), 7.16±7.38 (m, 10H, aryl-H), 7.68±7.74 (m, 2H, phenyl 3-H, 5-H), 8.09±8.16 (m, 2H, phenyl
2-H, 6-H) ppm.
6-(2-Chlorobenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9c; C23H15ClN2O3)
Prepared by method A in 65% and by method B in 66% yield; m.p.: 164±166ꢀC (ethanol); IR:
ꢁ ˆ 3070±3050 w, 1755 s, 1690 s, 1600 m, 1590 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 6.60 (s,
1H, 3-H), 7.22±7.40 (m, 10H, aryl-H), 7.54±7.63 (m, 1H, phenyl-H), 7.70±7.76 (m, 2H, phenyl-H),
8.12 (dd, J ˆ 7 and 1.5 Hz, 1H, phenyl-H) ppm.
6-(2-Bromobenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9d; C23H15BrN2O3)
Prepared by method A in 44% and by method B in 72% yield; m.p.: 104±108ꢀC (ethanol); IR:
ꢁ ˆ 3060±3040 w, 1745 s, 1685 s, 1595 m, 1585 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 6.61 (s,
1H, 3-H), 7.20±7.41 (m, 10H, aryl-H), 7.58±7.68 (m, 2H, phenyl-H), 7.84±7.93 (m, 1H, phenyl-H),
8.05±8.15 (m, 1H, phenyl-H) ppm.
6-(4-Chloro-2-nitrobenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9e; C23H14ClN3O5)
Prepared by method A in 84% yield; m.p.: 138±144ꢀC (ethanol); IR: ꢁ ˆ 3130±3010 wb, 1765 s,
1
1690 s, 1590 m, 1530 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.58 (s, 1H, 3-H), 7.20±7.42 (m,
10H, aryl-H), 8.03±8.10 (m, 1H, phenyl 5-H), 8.20 (d, J ˆ 8 Hz, 1H, phenyl 6-H), 8.40 (d, J ˆ 1.5 Hz,
1H, phenyl 3-H) ppm.
6-(4-Methylbenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9f; C24H18N2O3)
Prepared by method B in 72% yield; m.p.: 199±201ꢀC (1-butanol); IR: ꢁ ˆ 3100±2900 wb, 1740 s,
1
1690 s, 1605 m, 1520 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.42 (s, 3H, CH3), 6.58 (s, 1H, 3-
H), 7.18±7.40 (m, 10H, aryl-H), 7.45 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 8.04 (d, J ˆ 8 Hz, 2H,
phenyl 2-H, 6-H) ppm.
6-(4-Methoxybenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9g; C24H18N2O4)
Prepared by method B in 70% yield; m.p.: 188±190ꢀC (ethanol).
6-(2,4-Dichlorobenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9h; C23H14Cl2N2O3)
Prepared by method B in 82% yield; m.p.: 154±157ꢀC (ethanol); IR: ꢁ ˆ 3060 w, 1758 s, 1695 s,
1
1605 m, 1580 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.61 (s, 1H, 3-H), 7.19±7.42 (m, 10H,
aryl-H), 7.70 (dd, J ˆ 8 and 1.5 Hz, 1H, phenyl 5-H), 7.92 (d, J ˆ 2 Hz, 1H, phenyl 3-H), 8.18 (d,
J ˆ 8 Hz, 1H, phenyl 6-H) ppm.
6-(2,3-Dichloro-4-methylsulfonylbenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9i; C24H16Cl2N2O5S)
Prepared by method A in 23% yield; m.p.: 208±210ꢀC (ethanol); IR: ꢁ ˆ 3070 w, 1760 s, 1680 m,
1500 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 3.52 (s, 3H, SO2CH3), 6.68 (s, 1H, 3-H), 7.20±7.40
(m, 10H, aryl-H), 8.28 (m, 2H, phenyl-H) ppm.

Tricarbonylmethane Derivatives of N-Containing Heterocycles
881
6-(2-Methylbenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9j; C24H18N2O3)
Prepared by method B in 63% yield; m.p.: 143±145ꢀC (1-butanol); IR: ꢁ ˆ 3100±2880 w, 1750 s,
1
1680 m, 1590 m, 1515 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.64 (s, 3H, CH3), 6.60 (s, 1H,
3-H), 7.20±7.70 (m, 13H, aryl-H), 8.10 (dd, J ˆ 7 and 1.5 Hz, 1H, phenyl H) ppm.
6-(2-Methyl-3-methoxy-4-methylsulfonylbenzoyloxy)-2,3-diphenyl-4(3H)-pyrimidone
(9k; C26H22N2O6S)
Prepared by method A in 51% yield; m.p.: 174±179ꢀC (ethanol).
6-(2-Thienylcarbonyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9l; C21H14N2O3S)
Prepared by method A in 63% yield; m.p.: 168±172ꢀC (ethanol); IR: ꢁ ˆ 3070 w, 1730 s, 1685 s,
1
1510 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.58 (s, 1H, 3-H), 7.20±7.40 (m, 11H, 10 aryl-H,
thiophene 4-H), 8.08 (dd, J ˆ 6 and 1 Hz, 1H, thiophene 3-H), 8.19 (dd, J ˆ 6 and 1 Hz, 1H,
thiophene 5-H) ppm.
6-(3-Pyridylcarbonyloxy)-2,3-diphenyl-4(3H)-pyrimidone (9m; C22H15N3O3)
Prepared by method B in 32% yield; m.p.: 150±160ꢀC (toluene); IR: ꢁ ˆ 3060 w, 1755 s, 1680 s,
1
1590 s, 1545 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.53 (s, 1H, 3-H), 7.19±7.42 (m, 10H, 10
aryl-H), 7.65±7.75 (m, 1H, pyridine 5-H), 8.50 (m, 1H, pyridine 4-H), 8.95 (dd, J ˆ 7 and 1.5 Hz,
pyridine 6-H), 9.28 (d, J ˆ 1.5 Hz, pyridine 2-H) ppm.
5-Benzoyl-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10a; C23H16N2O3)
Prepared by method A in 82% yield; m.p.: 228±230ꢀC (ethanol).
5-(4-Chlorobenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10b; C23H15ClN2O3)
Prepared by method A in 38% and by method B in 52% yield; m.p.: 198±201ꢀC (ethanol); IR:
1
ꢁ ˆ 3060 w, 1700 s, 1590±1490 sb, 1450 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 7.20±7.48 (m,
10H, aryl-H), 7.57 (d, J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.92 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
5-(2-Chlorobenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10c; C23H15ClN2O3)
Prepared by method A in 74% yield; m.p.: 167±169ꢀC (ethanol); IR: ꢁ ˆ 3060 w, 1700 s, 1560 s,
1
1525 s, 1490 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 7.22±7.50 (m, 14H, aryl-H) ppm.
5-(2-Bromobenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10d; C23H15BrN2O3)
Prepared by method A in 78% yield; m.p.: 185±188ꢀC (ethanol); IR: ꢁ ˆ 3060 w, 1705 s, 1585 s,
1565 s, 1515 s cmꢁ1 1H NMR (200 MHz, ꢀ, DMSO-d6): 7.18±7.47 (m, 13H, aryl-H), 7.58 (d,
;
J ˆ 7 Hz, 1H, aryl-H) ppm.
5-(4-Chloro-2-nitrobenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10e; C23H14ClN3O5)
Prepared by method A in 72% and by method B in 66% yield; m.p.: 202±204ꢀC (toluene); IR:
1
ꢁ ˆ 3120±2840 wb, 1690 s, 1590 m, 1560 m, 1525 s cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 7.22±

882
B. Schnell and T. Kappe
7.51 (m, 11H, aryl-H, phenyl 5-H), 7.87 (dd, J ˆ 7 and 1.5 Hz, 1H, phenyl 6-H), 8.18 (d, J ˆ 1.5 Hz,
1H, phenyl 3-H) ppm.
5-(4-Methylbenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10f; C24H18N2O3)
Prepared by method A in 65% and by method B in 66% yield; m.p.: 218±221ꢀC (1-butanol); IR:
1
ꢁ ˆ 3050 w, 1705 s, 1590 s, 1450 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 2.41 (s, 3H, CH3),
7.23±7.50 (m, 12H, aryl-H), 7.88 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
5-(4-Methoxybenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10g; C24H18N2O4)
Prepared by method A in 50% yield; m.p.: 180±184ꢀC (1-butanol).
5-(2,4-Dichlorobenzoyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10h; C23H14Cl2N2O3)
Prepared by method A in 57% yield; m.p.: 153±156ꢀC (1-butanol); IR: ꢁ ˆ 1710 s, 1585 s, 1565±
1525 sb cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 7.22±7.52 (m, 12H, aryl-H), 7.60 (d, J ˆ 2 Hz, 1H,
phenyl 3-H) ppm.
5-(2-Thienylcarbonyl)-6-hydroxy-2,3-diphenyl-4(3H)-pyrimidone (10i; C21H14N2O3S)
Prepared by method A in 56% yield; m.p.: 235±238ꢀC (toluene); IR: ꢁ ˆ 3080 w, 1680 s, 1550 s,
1
1520 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 7.20±7.50 (m, 11H, aryl-H, thiophene 4-H), 7.90
(dd, J ˆ 6 and 1.5 Hz, 1H, thiophene 3-H), 8.02 (dd, J ˆ 6 and 1.5 Hz, 1H, thiophene 5-H) ppm.
5-Benzoyloxy-2-methyl-6-phenyl-3(2H)-pyridazinone (12a; C18H14N2O3)
Prepared by method B in 78% yield; m.p.: 147±150ꢀC (ethanol); IR: ꢁ ˆ 1750 s, 1670 s, 1610 w,
1
1595 w cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 3.78 (s, 3H, NCH3), 7.24 (s, 1H, 5-H), 7.38±7.43
(m, 3H, aryl-H), 7.54±7.80 (m, 5H, aryl-H), 8.02 (d, J ˆ 8 Hz, 2H, aryl-H) ppm.
5-(4-Chlorobenzoyloxy)-2-methyl-6-phenyl-3(2H)-pyridazinone (12b; C18H13ClN2O3)
Prepared by method B in 78% yield; m.p.: 125±126ꢀC (ethanol); IR: ꢁ ˆ 3070 w, 1755 s, 1660 s,
1
1590 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 3.78 (s, 3H, NCH3), 7.25 (s, 1H, 5-H), 7.35±7.45
(m, 3H, aryl-H), 7.58±7.71 (m, 4H, aryl-H), 7.96±8.20 (m, 2H, aryl-H) ppm.
5-(4-Methoxybenzolyoxy)-2-methyl-6-phenyl-3(2H)-pyridazinone (12c; C19H16N2O4)
Prepared by method B in 83% yield; m.p.: 163±165ꢀC (toluene); IR: ꢁ ˆ 1740 s, 1670 s, 1605 m,
1510 w cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 3.78 (s, 3H, NCH3), 3.87 (s, 3H, OCH3), 7.08 (d,
J ˆ 8 Hz, 2H, phenyl 3-H, 5-H), 7.20 (s, 1H, 5-H), 7.38±7.44 (m, 3H, aryl-H), 7.60±7.68 (m, 2H,
aryl-H), 7.96 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
5-Benzoyloxy-3-chloro-6-phenyl-pyridazine (15a; C17H11ClN2O2)
Prepared by method B in 78% yield; m.p.: 114±117ꢀC (toluene); IR: ꢁ ˆ 3050 w, 1755 s, 1600 m,
1580 w cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 7.47±7.68 (m, 5H, aryl-H), 7.74±7.88 (m, 3H, aryl-
H), 8.06 (dd, J ˆ 7 and 1.5 Hz, 2H, aryl-H), 8.38 (s, 1H, 4-H) ppm.

Tricarbonylmethane Derivatives of N-Containing Heterocycles
883
3-Chloro-5-(4-chlorobenzoyloxy)-6-phenyl-pyridazine (15b; C17H10Cl2N2O2)
Prepared by method B in 75% yield; m.p.: 135±137ꢀC (toluene); IR: ꢁ ˆ 3150 w, 1755 s, 1595 m,
1558 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 7.44±7.55 (m, 3H, aryl-H), 7.68 (d, J ˆ 8 Hz, 2H,
phenyl 3-H, 5-H), 7.80±7.90 (m, 2H, aryl-H), 8.06 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H), 8.38 (s, 1H,
4-H) ppm.
3-Chloro-5-(4-methoxybenzoyloxy)-6-phenyl-pyridazine (15c; C18H13ClN2O3)
Prepared by method B in 79% yield; m.p.: 151±154ꢀC (toluene); IR: ꢁ ˆ 3160±2980 wb, 1740 s,
1610 s, 1580 w cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 3.88 (s, 3H, OCH3), 7.12 (d, J ˆ 8 Hz, 2H,
phenyl 3-H, 5-H), 7.46±7.54 (m, 3H, aryl-H), 7.80±7.88 (m, 2H, aryl-H), 8.01 (d, J ˆ 8 Hz, 2H,
phenyl 2-H, 6-H), 8.34 (s, 1H, 4-H) ppm.
4-Benzoyl-3-cyano-5-hydroxy-6-phenyl-pyridazine (16; C18H11N3O2)
To a solution of 2.06 g 11 (10 mmol) in 60 ml of dry toluene, 1.4 ml benzoylchloride (12 mmol) and
1.4 ml Et3N (10 mmol) were added. The solution was heated for 6 h under re¯ux. After cooling to
room temperature, 1.3 g KCN (20 mmol), 1.4 ml Et3N (10 mmol), and catalytic amounts (0.4±0.5 g)
of 18-crown-6 were added. The reaction mixture was stirred for 72 h at room temperature. At the end
of the reaction, 80 ml of CH2Cl2 were added, and the mixture was washed several times with dilute
HCl in a separatory funnel. 16 precipitated from the aqueous solution during drying the organic
phase over Na2SO4. Removing the solvent by evaporation yielded the starting material 14.
Yield of 16: 0.56 g (19%); m.p.: 209±212ꢀC (ethanol); IR: ꢁ ˆ 3320±3170 m, 3060 w, 2240 s,
1
1690 s, 1615 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 7.56±7.76 (m, 6H, aryl-H), 7.93±8.12 (m,
4H, aryl-H), 12.38 (s, 1H, OH) ppm.
General procedure for the synthesis of 2-benzoyl-5-benzoyloxy-1-phenyl-3(2H)-pyrazolones 18a±e
To a solution of 5-hydroxy-1-phenyl-3(2H)-pyrazolone (6, 10 mmol) in 70 ml of dry toluene, the
corresponding acid chloride 2 (22 mmol) and Et3N (20 mmol) were added. The solution was heated
for 7 h under re¯ux. After cooling to room temperature, 100 ml CH2Cl2 were added, and the mixture
was washed several times with dilute HCl in a separatory funnel. The organic phase was dried over
Na2SO4, and the solvent was removed by evaporation.
2-Benzoyl-5-benzoyloxy-1-phenyl-3(2H)-pyrazolone (18a; C23H16N2O4)
From 1.76 g 6 and 2.6 ml benzoylchloride; yield: 53%; m.p.: 110±111ꢀC (ethanol); IR: ꢁ ˆ 1765 s,
1
1748 s, 1600 m, 1590 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.65 (s, 1H, 4-H), 7.38±7.85 (m,
11H, aryl-H), 8.08±8.23 (m, 4H, aryl-H) ppm.
2-(4-Chlorobenzoyl)-5-(4-chlorobenzoyloxy)-1-phenyl-3(2H)-pyrazolone (18b; C23H14Cl2N2O4)
From 1.76 g 6 and 3.0 ml 4-chlorobenzoylchloride; yield: 66%; m.p.: 168±170ꢀC (ethanol); IR:
1
ꢁ ˆ 1770 w, 1760 m, 1745 s, 1595 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.65 (s, 1H, 4-H),
7.38±7.78 (m, 9H, aryl-H), 8.05±8.22 (m, 4H, aryl-H) ppm.
2-(2-Chlorobenzoyl)-5-(2-chlorobenzoyloxy)-1-phenyl-3(2H)-pyrazolone (18c; C23H14Cl2N2O4)
From 1.76 g 6 and 2.9 ml 2-chlorobenzoylchloride; yield: 56%; m.p.: 105±107ꢀC (ethanol); IR:
1
ꢁ ˆ 1775 s, 1590 m, 1560 m, 1505 m cmꢁ1; H NMR (200 MHz, ꢀ, DMSO-d6): 6.67 (s, 1H, 4-H),
7.37±7.74 (m, 11H, aryl-H), 8.11 (t, J ˆ 7 Hz, 2H, aryl-H) ppm.

884
B. Schnell and T. Kappe
2-(4-Methylbenzoyl)-5-(4-methylbenzoyloxy)-1-phenyl-3(2H)-pyrazolone (18d; C25H20N2O4)
From 1.76 g 6 and 3.0 ml 4-methylbenzoylchoride; yield: 61%; m.p.: 181±185ꢀC (toluene); IR:
ꢁ ˆ 3170 w, 1750 s, 1738 s, 1615 m, 1600 m cmꢁ1; 1H NMR (200 MHz, ꢀ, DMSO-d6): 2.49 (m, 6H, 2
CH3), 6.63 (s, 1H, 4-H), 7.42±7.77 (m, 9H, aryl-H), 8.00±8.15 (m, 4H, aryl-H) ppm.
2-(2,4-Dichlorobenzoyl)-5-(2,4-dichlorobenzoyloxy)-1-phenyl-3(2H)-pyrazolone
(18e; C23H12Cl4N2O4)
From 1.76 g 6 and 3.08 ml 2,4-dichlorobenzoylchloride; yield: 52%; m.p.: 148ꢀC (ethanol); 1H NMR
(200 MHz, ꢀ, DMSO-d6): 6.63 (s, 1H, 4-H), 7.27±7.62 (m, 9H, aryl-H), 7.88 (d, J ˆ 8 Hz, 1H, aryl-
H), 8.12 (d, J ˆ 8 Hz, 1H, aryl-H) ppm.
2,4-Di-(4-chlorobenzoyl)-5-hydroxy-1-phenyl-3(2H)-pyrazolone (19a; C23H14Cl2N2O4)
A mixture of 2.26 g 18b (5 mmol), 0.7 ml Et3N (5 mmol), 0.68 g KCN (10 mmol), and catalytic
amounts (0.3±0.4 g) of 18-crown-6 in 50 ml of dry toluene was stirred for 48 h at room temperature.
After addition of 70 ml CH2Cl2, the reaction mixture was washed several times with dilute HCl in a
separatory funnel. The organic phase was dried over Na2SO4, and the solvent was removed by
evaporation.
Yield: 1.25 g (55%); m.p.: 167±170ꢀC (ethanol); IR: ꢁ ˆ 1758 s, 1612 m, 1595 s, 1560 s cmꢁ1
;
1H NMR (200 MHz, ꢀ, DMSO-d6): 7.28±7.95 (m, 13H, aryl-H) ppm.
2,4-Di-(4-methylbenzoyl)-5-hydorxy-1-phenyl-3(2H)-pyrazolone (19b; C25H20N2O4)
Form 1.24 g 18d (3 mmol) according to the preparation of 19a.
Yield: 1.10 g (89%); m.p.: 163±167ꢀC (ethanol); IR: ꢁ ˆ 1748 s, 1610 s, 1560 s, 1455 m cmꢁ1
;
1H NMR (200 MHz, ꢀ, DMSO-d6): 2.18 (s, 3H, CH3), 2.42 (s, 3H, CH3), 7.13 (d, J ˆ 8 Hz, 2H, aryl-
H), 7.30±7.44 (m, 3H, aryl-H), 7.50±7.63 (m, 4H, aryl-H), 7.70±7.82 (m, 4H, aryl-H) ppm.
References
[1] White PS, Findlay JA, Tam HJ (1978) Can J Chem 56: 1904; Girotra NN, Wendler NL (1979)
Tetrahedron Lett 493; see also Ref [2] No. F-00041, p 437
[2] Southon IW, Buckingham J (ed) (1989) Dictionary of Alkaloids, 1st edn. Chapman & Hall,
London New York, No. R-00072, p 923
[3] The Merck Index, 12th edn, Merck & Co Inc, Rahway, NJ (1996) No. 8377, p 1412
[4] See Ref [2]: No. B-00056, p 135; Wat CK, Molnes AG, Smith DG, Wright JLC (1977) Can J
Chem 55: 4090
[5] See Ref [2]: No. T-00055, p 1028; Williams DR, Sit SY (1982) J Org Chem 47: 2846; Cox R,
O'Hagan D (1991) J Chem Soc Perkin Trans 1, 2537
[6] See Ref [2]: No. I-00015, p 560; Matsumoto M, Minato H (1976) Tetrahedron Lett 36: 3827
[7] Ando K, Matsuura I, Nawata Y, Endo H, Sasaki H, Okutomi T, Saeki T, Tamura G (1976)
J Antibiot 31: 533; Nawata Y, Marsuura I, Ando K, Iitaka Y (1990) Acta Crystallogr Sect C
46: 515
[8] Trecourt F, Mallet M, Mongin O, Quegeuiner G (1995) J Heterocylic Chem 32: 1117; Cutler HG,
Jacyno JM (1991) Agric Biol Chem 55: 2629
[9] Kim JC, Lee YW, Tamura H, Yoshizawa T (1995) Tetrahedron Lett 36: 1047
[10] Antibiotic MYC 8003; see Ref [3]: No. 6308, p 1065; Maehr H, Leach M, Williams TH, Blount
JF (1980) Can J Chem 58: 501

Tricarbonylmethane Derivatives of N-Containing Heterocycles
885
[11] Iwataki I (1992) Rational Apporaches to Structure, Activity, and Ecotoxicology of Agrochem-
icals, Draber W, Fijita T (ed) CRC Press, Boca Raton, pp 397±426
[12] Kappe T, Schnell B (1996) J Heterocyclic Chem 33: 663
[13] Kappe T, Aigner R, Hohengassner P, Stadlbauer W (1994) J Prakt Chem 336: 596, and literature
cited therein
[14] Faber K, Kappe T (1984) J Heterocylic Chem 21: 1881; Kappe CO, Kappe T (1989) J
Heterocyclic Chem 26: 1555
[15] Roschger P, Stadlbauer W (1990) Liebigs Ann Chem 821; Roschger P, Fiala W, Stadlbauer W
(1992) J Heterocyclic Chem 29: 225
[16] For anionic Fries rearrangement see: Sibi MP, Snieckus V (1983) J Org Chem 48: 1935; Wang W,
Snieckus V (1992) J Org Chem 57: 424
[17] Tabuchi H, Hamamoto T, Ichihara A (1993) Synlett 651
[18] Oliver JE, Wiltzer KR, Waters RM (1990) Synthesis 1117; Oliver JE, Lusby WR (1991) J
Heterocyclic Chem 28: 1565
È
[19] Kappe T, Aigner R, Jobstl M, Hohengassner P, Stadlbauer W (1995) Heterocyclic Commun 1:
341
[20] Hansen PE, Bolvig S, Kappe T (1995) J Chem Soc Perkin Trans 2, 1901
[21] Henze HR, Clegg WJ, Smart CW (1952) J Org Chem 17: 1320
[22] Collie JN (1891) J Chem Soc (London) 59: 607; Butt MA, Elvidge JB (1963) J Chem Soc
(London) 4483; Castillo S, Quadahi H, Herault V (1982) Bull Soc Chim France 257
Received April 8, 1998. Accepted (revised) May 4, 1998