Note: Descriptions are shown in the official language in which they were submitted.
~3~4
The inventian is concerned with a novel process for production of 4-
substit~lted 1,2-diphenyl-3,5-dioxopyrazolidines of general formula
R \ / CO- N ~ - A
/ 2 \ ¦ ~ I
where R and R', which may be id ntical to or different from each other, repre-
sent a hydrogen atom, a lower aIkyl group, a phenyl group or the group -COOR"
(where R" means hydrogen or a lower aIkyl group) and A a hydrogen atom or a
hydroxyl group. Compound~s of general formula I exist in the so-called Z- and in
the isomeric E-form, which fall both under the general formula designated above
(as well as mixtures thereof).
From British Patent 1 301 857 it has already been known that, amcng
others, compounds of general formula I are valuable antiphlogistically active
compounds, which are superior to the butazolidine - simLlar to them in structure
- as far as the main actian and the absence of side effects are concerned.
There have been described as well several processes for prcduction of these oomr
pounds.
It has been found now, that oompounds of general formula I are also
produced by reacting a cyclosemiacetal of general formula
D
CH2 C - 00--N ~
where A' represents hydrogen or an etherified hydroxyl group, preferably the
-- 1 --
L~
'~
~. .
.. ~ . . ..
~: :
.
.
1~3~
~-methoxyethoxymethoxy (=0-MEM) group, with a triarylphosphorane derivative of
general formula
R \ / Ar
C = P \ Ar III
R' Ar
where R and R' have the above-mentioned meanings and Ar represents a phenyl
group (optionally substituted with an inert group such as methyl, methoxy or
phenyl) and, subsequently, optionally liberating the etherified hydroxyl grollp
by means of a mild Lewis-acid. As suitable Lewis-acids may be considered TiC14
and ZnBr2, but ZnC12, ZnJ2, SnCL4, SnBr4, MgBr2 and similar metal halides as
well.
Reaction of the compounds II and III may be effected within an aprotic
solvent such as dimethylfoxmamide or, preferably, dimethylsulfoxide under
anhydrous conditions.
Instead of the cyclosemlacetals of general formula II, there may be
used in the reaction, in case A represents hydrogen, also the aldehyde of
general formula
H \ / CO N ~
C - CH2 - CH \ ¦ ~ IIa
on which they are based.
The oc~pounds of formula III may also be produced insitu from the
corresponding, saturated phosphonium salt of general formula
R / Ar
( )
/ CHP \ Ar X IIIa
Rl Ar
-- 2 --
~, ~
113~t~34
where R, R' and Ar have the meanings mentioned above and X( ) represents a
halogen ion, by splitting off hydrogen halide by means of a suitable metal rea-
gent, such as, for example, sodium hydride, sodium amide, butyl-lithium or
phenyl lithium.
The process may be effected in such a way, that the reaction mixture -
after stirring at room temperature - is heated to a temperature between 30 and
loo&, preferably at 50 to 70&, then it is allowed to cool off and stirred
afterwards at room temperature.
After the reaction has been finished, the reaction mixture may be
worked up by pouring it on ice, extracting with a suitable organic solvent such
as ethylacetate, or dichloromethane and column-chrcmatography, or else reextrac-
tion of the organic solvent with a basic, aqueous medium. In the latter case,
the product will only be obtained after acidification with a mineral acid (for
example hydrochloric acid) and extraction with a suitable solvent. Additional
purification as well as separation of the geometrical (E,Z)-isomers may be ab-
tamed by column-chromatography.
If in the starting co~pounds A represents an etherified hydroxyl group,
this OH group protected during the reaction must subsequently be liberated in
order to abtain compounds of form~la I with A = OH. This may, for example, be
carried out in such a way, that the etherified OH group, converted, for example,
into the ~-methoxyethoxymethyl (=MEM)- ether, is split off after the finished
reaction of the etherified cyclosemiacetal II with the triphenyl phosphorane
derivative of formula III with mild Lewis-acids (for example TiC14 in dichloro-
methane).
The compounds of formLla I, where R is CH3 and R' is C0OH, are ob-
tained by mild alkaline saponification of the corresponling esters (R = CH3,
R' = COOR").
113~34
The compounds of general formula II may be obtained in a simple way
by rearr~mgement of the corresponding cyclic acetals of general formula
CH2- - 0 / C0 - N - ~ - A'
CH - CH2 - CH IV
( H2__ o/ CO I ~ ~
where A' has the meanings indicated above. This rearrangement may be effected,
for example, by means of simple heating in aqueous ethanol.
The compounds of general formula IV in their turn may be obtained
by reacting diethyl 2-(2-ethylenedioxyethyl)malonate of formula
CH - 0 C2 5
I CH ~ CH2 ~ CH \ V
CH ~ 0 COOC2H5
with hydrazobenzene or an etherified p-hydroxyhydrazobenzene such as hydrazo-
benzene-~ methoxyethoxymethyl-(=MEM)-ether, in the presence of a suitable
condensing agent such as a solution of sodium in anhydrous ethanol.
The compound of formula V may be obtained by measures known per se,
for example by condensation of 2-ethylenedioxyethylbromide with diethylmalonate
in the benzene/dimethylformamide in the presence of sodium hydride.
The aldehydes of formula IIa may be obtained by deketalizing of the
compound of formula IV with A' = hydrogen; deketalization may be effected, for
example, within anhydrous dichloromethane with borotribromide.
The process according to the invention runs smoothly and results in
high yields without substantial amounts of side products, as the introduction of
the double bond takes place as envisaged and the formation o~ disubstituted
products at C-4 of the pyrazolidine ring is avoided.
-4-
1~3~83~
The follcwing examples illustrate the invention without restricting
its sccpe:
Exan~
F~Hydro ~ azobenzene-~-methoxyethQ~methylether(MEM)
To a stirred suspension of 66.14 g (1.516 mol) of sodium hydride (55%
dispersion in mineral oil) in tetrahydrofuran (400 ml) is added dropwise a solu-
tion of p-hydroxyazobenzene (191 g, 0.963 mol) in 810 ml of tetrahydrofuran.
After having stirred for 15 minutes the solution is cooled off. Then are
dropped in at o& 144 g (1.156 mol) MEM}chloride (E.J. Corey, J.L. Gras and P.
Ulrich, Tetrahedron Lett.t 809 (1976)) and the mixture is stirred for 30 minutes
at this temperature. Stirring is continued for one hour at room temperature,
the excess sodium hydride is decomposed under the a~;tion of water and the mix-
ture is evaporated in vacuo. The residue is taken up in ether and washed
suc oe ssively with water, 5% sodium hydroxide and water until it remains neutral.
The ether extract is dried and evaporated under decreased pressure. In doing so,
the title oompound is formung as thick, reddish oil (271.44 g 98%), which is
used without further purification.
Exa~ple 2
p-Hydroxyhvdrazokenzene-MEM~ether
A solution of p,hydroxyazobenzene-MEM-ether (220 g, 0.768 mol) in 1300
ml of ethanol is hydrogenated in the presen oe of 2.2 g Pd/C at room temperature
and atmospheric pressure. After absorbing the calclllated quantity of hydrogen,
the solution is filtered and evaporated until 220 g (99%) of a thick, yellow oil
remains that has been used again immediately in the next step due to its easy
oxidizability.
-- 5 --
113'~834
Example 3
Diethyl-2-~2-ethylenedioxyethyl)-malonate
To a stirred suspension of 141.38 g (3.24 mol) of sodium hydride (55%
dispersion in mineral oil) in dimethylformamide (1300 ml) and benzene (500 ml) is
added dropwise diethylmalonate (471.8 g, 2.94 mol). After stirring at room
temperature until the H2-develcpment is finished, 2-ethylenedioxyethyIbromide
(S.M. Gurvich Zh. Obshch. Khim., 27, 2888(1957) (492 g, 2.94 mol) is added in
500 ml of benzene and the solution is stirred for 16 hours at 80&. Then, the
mixture is cooled off, poured into excess ice-w~ater and the product is isolatedwith ether. After evaporation of the dried extract, 2-(2-ethylenedioxyethyl)-
malonate is obtained.
Boiling point 105 - 108C (0,5 mm).
Analysis for
CllH18O6: found: % C 53.42 H 7.42
calcul. % C 53.65 H 7.37
Example 4
4-(2-Ethylenedioxyethyl)-1,2-diphenyl-3,5-dioxopyrazolidine
Hydrazob~nzene (58.4 g, 0.317 mol) is added while stirring to a sodium
solution (8.02 g, 0.348 mol) in 480 ml of anhydrous ethanol, then diethyl-2-
(2-ethylenedioxyethyl)-malonate (78.05 g, 0.317 mol) is drcpped in during 2
hours at reflux temperature. Additionally, the mixt~lre is heated for one hour,
the solvent is gradually evaporated to dryness and the residue heated under de-
creased pressure (15 mm) for one hour at 130 to 140 &. m e reaction prcduct is
cooled, taken up in water, washed with ether and filtered w~ith active charcoal.While oooling the solution is acidified. This yields a white solid material
(72.95 g, 68%), is dried in vacuo over phosphorus pentoxide and is used without
further purificatian in the next step.
113~ii3~
Melting point: 150 C.
Analysis for
ClgH18N2C)4: found ~ C 67.71H 5.33 N 8.23
calc. % 67.44 5.36 8.28
Example 5
.
4-(2-Ethylenedioxyethyl)-l-(ptMEM~oxyphenyl)-2-phenyl-3,5-dioxopyrazolidine
p-Hydroxyhydrazobenzene-MEM~ether (137 g, 0.475 mol) in 140 ml of
anhydrous ethanol is added while stirring to a solutian of sodium (1092 g,
0.475 mol) in ethanol (330 ml) and then diethyl-2-(2-ethylenedioxyethyl)-
malonate (117 g, 0.475 mol) in 120 ml of ethanol is drcpped in under reflux
temperature during 2 hours. Then, the mixture is refluxed for 1 hour more, the
solvent is evaporated gradually to dryness and the residue is heated under de-
creased pressure for 1 hour to 130 to 140 &. The reaction prcduct is ccoled,
taken up in water, washed with ether and filtered over active charcoal. The
solution is acidified with 10% hydrcchloric acid to pH4 and the separating oil
is extracted with ethylaoetate. The dried extract that is evaporated to dryness
leaves an oily residue the latter being dissolved in a saturated solution of
piperazine in aoe tone. The crystallized piperazine salt of the 4-(2-ethylene-
dioxyethyl)-l-(p-MEM~oxyphenyl)-2-phenyl-3,5-dioxopyrazolidine, which separated
while standing is filtered and then dissolved in water. After acidifying with
glacial aoe tic acid the product is isolated with ether. When evaporating the
dried extract, the desired pyrazolidine formed as slightly yellow oil (105 g,
50%), which is pure enough to be converted into 1,2,4,5-tetrahydro,l-(p-MEM~
oxyphenyl)-2-phenyl-3H-5-hydroxy-furo[2,3-c]-pyrazole-3-ane.
Example 6
1,2,4,5-Tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo[2,3-c]-pyrazole-3-one
A solution o~ 4-(2-ethylenediaxyethyl)-1,2-diphenyl-2,5~diQxo-
li3'~3~
pyrazolidine (51.36 g, 0.152 mDl) in 510 ml of 50% aqueous ethanol is refluxed
for 3 hours. The solid naterial that crystallizes out of the still hot solution,
is collected by means of filtering and dried in vacuo. 36.66 g (82~) of the
1,2,4,5--tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo-[2,3-c]pyrazole-3-one are ob-
tained.
Melting point: 267 C decomposition.
Analysis for
C17H14N2O3: found % C 69.18 H 4.75 N 9.63
calc. % 69.37 4.809.52
Examele 7
1,2,4,5-Tetrahydro-l-(p-MEM~oxyphenyl)-2-phenyl-3H-5-hydroxy-furo[2,3-c]-
pyrazole-3-one
A solution of 4-(2-ethylenedioxyethyl)-1-(p-MEM~oxyphenyl)-2-phenyl-
3,5-dioxopyrazolidine (130 g, 0.294 1) in 1200 ml of 75~ ethanol is refluxed
for 6 hours and then evaporated to dryness. The obtzined residue is recrystal-
lized from ethylaoe tate and yields 66 g (56%) of the 1,2,4,5-tetrahydro-1-
(p-MEM~oxyphenyl)-2-phenyl-3H-5-hydroxy-furo[2,3-c]pyrazole-3-one as colourless
crystal.
Melting point: 203 C decomposition.
Analysis for
C21H22N2&: found % C 62.99 H 5.49 N 6.95
calc. % 63.31 5.57 7.03
Example 8
4-(2-Formylmethyl)-1,2-diphenyl-2,5-dioxopyrazolidine
To a solution of 4-(2-ethylenedioxyethyl)-1,2-diphenyl-3,5-dioxo-
pyrazolidine (2.54 g, 7.5 mol) in 400 ml of dichloromethane is added a solution
of borotribromide (18.79 g, 75 mol) in 50 ml of dichloromethane at -70 & drop-
~.i
~ , .
1134~34
wise while stirring. At this temperatuLe stirring is continued for 24 hours.Then the temperature is allowed rise to room temperature and the mixture is
poured on excess ice-water.
The organic layer is separated and washed (NaHCO3-solution) until it
is neutral, dried (M~SO4) and evaporated to dryness.
The viscous residue is crystallized frcm ethylether-dichlorcmethane
(8:2) and yields 0.7 g (3147%) of the desired pyrazolidine as colourless solid.
Melting point: 240 - 242 C.
Analysis for
C17H14N2O3: found ~ C 69.54H 4.92 N 9-44
calc. ~ 69.37 4.80 9.52
Example 9
4-(3-Methyl-2-butenyl)-1,2-diphenyl-2,5-dioxopyrazolidine
A solution of isopropyl-triphenylphosphoniumiodide (45.24 g, 0.1 mDl)
[G. Wittig and D. Wittenberg, Ann., 606, 1 (1957)] in 180 ml of dimethyl-
sulfoxide is ad~ed dropwise to a stirred suspension of sodium methylsulfinyl
methide at 20 to 25 & (R. Greenwald, M. Chaykovsky and E.J. Corey, J. Org. Chem.,
28, 1128 (1963)), that has been prepared in situ from 4.15 g (0.095 mol) of a
55% dispersion of sodium hydride in mineral oil and 120 ml of dimethylsulfoxide.
The mixture is stirred for 30 mlnutes at room temperature and then 1,2,4,5-
tetrahydro~l,2-diphenyl-3H-5-hydroxy-furo[2,3-c]pyrazole-3-one (14 g, 0.047 mol)
is added in portions. The mixture is stirred for 2 hours at room temperature
and for a further hour heated to 70&.
After stirring at room temperature for 16 hours, the reaction mixture
is poured into exoess water and extracted with dichlorcmethane. The organic
phase is separated, washed with water, dried cver MgS04 and then evaporated to
dryness. The obtained residue is dissolved in benzene and adsorbed on a
_ g _
'
. . ..
...
'.
113~4
silicagel column. The elution with 10% aoe tone in benzene yields 8.79 g (58.4%)
of the desired pyrazolidine as colourless solid.
Melting point: 155 - 157 &.
Analysis for
C20H20N2O2: found % C 75.20H 6.23 N 8.64
calc. % 74.98 6.29 8.74
Example 10
4-(2-Propenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
This oompound is produced in a similar manner as described in example
9, by starting from 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo[2,3-c]-
pyrazole-3-one (5.88 g, 0.02 mol) and methyltriphenylphosphoniumiodide [C.H.
Collins and G.S. Hammcnd, J. Org. Chem., 25, 1434 (1960)] (17.78 g, 0.044 mol),
using sodium methylsulfinylmethide (0.04 mol) in dimethylsulfoxide (prepared as
described above). The title compc~nd is obtained after column-chromatography on
silicagel (10% aoetone in benzene) as colourless solid (64.5%).
Melting point: 133 - 135C (EtOH 95~).
Analysis for
C18H16N202: found % C 74.12 H 5.63 N 9.37
calc. % 73.95 5.529.58
Example 11
(E,Z)-4-(2-butenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
This oompound is produoed as described in example 9, starting from
1,2,4,5-tetrahydro-1,2-diphenyl-3~1-5-hydroxy-furo[2,3-c]-pyrazole-3-one (5.88 g,
0.02 mol) and ethyltriphenylphosphone bromide (16.33 g, 0.044 mol) [G. Wittig
and D. Wittenberg Ann., 606, 1 (1957)], using sodium methylsulfinylmethide
(0.04 mol) in dimethylsulfoxide prepared as described above. The compcNnd is
obtained after column-chromatography on silicagel (10% aoetone in benzene) as
-- 10 --
113~834
mixture of the E- and Z-forms, wherein the Z-iso~ere is prevailing (60%).
Melting point: 167 & (EtOH/H2O 1:1) literature melting p~int: 128& for the
compcund, obtained in the conventional malonate-hydrazobenzene way.
Analysi!3 for
ClgH18N2O2 fcund % C 74.32 H 5.87 N 9.22
calc. % 74.49 5.92 9.15
Example 12
(E,Z)-4-(3-phenyl-2-prGpenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
This compound is produced as described in example 9, starting from
1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo[2,3-c]-pyrazole-3-one (5.88 g,
0.02 mol) and benzyltriphenylphosphone chloride (17.11 g, 0.044 mol) [G. Wittig
and M. Schollkopf, Chem. Ber. 87, 1318 (1954)], using sodium methylsulfinyl-
methide (0.04 mol) in dimethylsulfoxide, as described above. The co~pound is
obtained as crude material in a yield of 64%.
The Z- and E-forms may be separated by column-chromatography on
~ilicagel (10% aoe tone in benzene).
(Z)-isomere: melting point 124 C (EtOH 95).
Analysis for
C24H20N2O2: found % C 78.29 H 5.31 N 7.48
calc. % 78.23 5.47 7.60
(E)-isomere: melting point 133 C (EtOH 95)
C24H20N2O2: found % C 78.42 H 5.54 N 7.46
calc. % 78.23 5.47 7.60
Example 13
(E,Z)-4-(3-carbethoxy-2-butenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
~ mixture of ~-carbethoxyethylidene-triphenylphosphorane O. Isler,
Helv. Chim. Acta, 40, 1241 (1957) (63.53 g, 0.175 mol) and 1,2,4,5-tetrahydro-
34
1,2-diphenyl-3H-5-hydroxy-furo[2,3-c]-pyrazole-3-one (26 g, 0.088 mol) in 400 ml
of anhydrous dimethylsulfo~ide is stirred for one hour at roam temeerature and
for another hour to 60C. After the reaction mixture has been stirred for 15
hours at room temperature, it is poured into excess water and extracted with
ethylacetate. The organic phase is separated and extracted several times with
an aqueous 5% piperazine solution. The united aqueous extracts are acidified to
pH 8 with 10% hydrochloric acid and the waxlike solid that separated is filtered
off and abandoned. me fil~ered solution is treated with charcoal, acidified to
pH 5.5 and extracted with ethylacetate. After evaporation of the dried extract,
the crude isomeric mixture of th,e OE)- and (Z)-4-(3-carbethoxy-2-butenyl)-1,2-
diphenyl-3,5-dioxopyrazolidine is obtained as a brawn, thick oil, which is dis-
solved in aoetone and purified by its 2-amino-2-thiazoline salt. The working up
of this salt, effected as described in example 5, delivers after extraction with
ethylaaetate and evaporation of the dried extract 19.5 g of an oily mixture of
the desired pyrazolidine, wherein the (E)-form prevailed. The mixture is dis-
solved in benzene and adsorbed on a silicagel column. The elution with 10%
ethylaoe tate in benzene yields 1.36 g (4%) of the (Z)-form as colourless solid.
Melting point: 151C.
Analysis for
C22H22N204: found % C 69.59 H 5.97 N 17.02
calc. % 69.82 5.86 16.91
Further elution with the same agent yields an intermediate fraction
oonsisting of a mixture of 2 isomeres, and then a fraction of 14 g (42%) of the
(E)-form as colourless solid, which is recrystallized from cyclohexane.
Melting point: 93C.
- 12 -
113~834
Example 14
(E,Z)-4-(3-carbethoxy-2-butenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
The compound is produoe d as described in example 13, starting frcm
u-carbethoxyethylidene triphenylp~osphorane (1.46 g, 4 mol) and 4-(2-formyl-
methyl)-1,2-diphenyl-3,5-dioxopyrazolidine (0.59 g, 2 mDl) in 12 ml of dimethyl-
sulfo~ide, whereby 0.24 g (31.7%) of the title compcNnd is obtained. The
physico-chemical and analytical data and also the E/Z-isomeres-proportion are
almDst identical to the data obtained in the previous example.
Example 15
(E,Z)-4-(3-car~ethoxy-2-butenyl)-1-(p-MEM~oxyphenyl)-2-phenyl-3,5-dioxo-
pyrazolidine _
A mixture of ~-carbethoxyethylidene triphenylphosphorane (14.49 g,
0.04 mol) and 1,2,4,5-tetrahydro-1-(p-MEM~oxyphenyl) 2-phenyl-3H-5-hydroxy-furo
[2,3-c]-pyrazole-3-one (15.96 g, 0.04 mol) in 90 ml of anhydrous dimethyl-
sulfoxide is allowed to react as described in example 13. Then, the reaction
mixture is poured into exoess water, extracted with ethylaoetate and extracted
once mDre with 5% aqueous piperazine solution. After acidifying the aqueous
phase to pH 6, the product is isolated with ether and yields, after evaporation
of the dried extract, 10.2 g of an oily mixture of the desired pyrazolidine,
wherein the (E)-form prevailed. The mixture is dissolved in benzene and ad-
sorbed at a silicagel column. me elution with dichloromethane yields 0.58 g
(3%) of the (Z)-form as yellow oil. After a fraction oonsisting of a mixture of
2 isomeres, the further elution yields a fraction of 6.05 g (31%) of the (E)-
isomere as yellow oil.
- 13 -
'` '~` :
:'
113~34
Example 16
(E)-4-(3-carbethoxy-2-butenyl)-1-(p-hydroxyphenyl)-2-phenyl-3,5-dioxo-
pyrazolidine
To a stirred solution of titanium tetrachloride (77.26 g, 0.407 mDl)
in 750 ml of dichlorc~ethane is added dropwise at o& a solution of (E)-4-
(3-carbethoxy-2-butenyl)-1-(p-MEM-oxyphenyl)-2-phenyl-3,5-dioxopyrazolidine, pre-
pared as described in example 15, (39.3 g, 0.081 mol) in 400 ml of dichloro-
methane. Stirring is continued for 1 hour and the mixture is poured into excess
ioe-water. The organic phase is separated and yields an oily residue, dissolved
in dichloromethane and adsor~ed on a silicagel column. The elution in 10%
methanol in dichloromethane yields 25.4 g (79%) of the title cowpound as colour-
less solid.
Melting point: 70 to 74 &~
Analysis for
C22H22N2O5: found ~ C 66.84H 5.51 N 6.92
calc. % 66.99 5.62 7.10
Example 17
(E)-4-(3-carboxy-2-butenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
A solution of (E)-4-(3-carbethoxy-2-butenyl)-1,2-diphenyl-3,5-dioxo-
pyrazolidine, prepared as described in example 13, (2.25 g, 5.28 mol) in 10 ml
of 10% sodium hydroxide is stirred for 30 minutes at room temperature and then
acidified with 10~ hydrochloric acid. The precipitating product is isolated
with dichloromethane and yields, after evaporation of the dried extract, a
viscous residue which is recrystallized from ethylether (1.05 g, 56.75%).
Melting point: 141&.
Analysis for
C20H18N2O4: found % C 68.28 H 5.19 N 7.97
calc. ~ 68.56 5.18 8.00
~i3~34
Example_l
~Z)-4-(3-carboxy-2-butenyl)-1,2-diphenyl-3,5-dioxopyrazolidine
This compound is prcduoe d as described in example 17, by means of
hydrolyz my the (Z)-4-(3-carbethoxy-2-butenyl)-1,2-diphenyl-3,5-dioxo-
pyrazolidine, prepared as described in example 13 (1 g, 2.6 mol) with 10% sodium
hydroxide (20 ml). After working up in the conventional way, the campound is
crystallized from ethylether and yields 0.6 g (61%) of the desired pyrazolidine
as colourless crystals.
Melting point: 65&.
Analysis for
C20H18N2O4: found % C 68.37H 5.28 N 7.88
calc. % 68.56 5.28 7.88
Example 19
(E)-4-(3-carboxy-2-butenyl)-1-(p-hydroxyphenyl)-2-phenyl-3,5-dioxopyrazolidine
The oompound is prepared m a similar manner by hydrolysis of the
~E)-4-(3-carbethoxy-2-butenyl)-1-(p-hydroxyphenyl)-2-phenyl-3,5-dioxopyrazolidine,
which is prepared as descr;h~d in example 16 (10 g, 25 mol) with 10% sodium
hydroxide (200 ml). The obtained ccmpound is recrystallized from acetanitrile.
This yields 2.15 g (23.2%) of the title compound as colourless crystals.
Melting point: 170 &.
Analysis for
C20H18N2O5: found % C 65.30H 5.01 N 7.61
calc. % 65.56 4.95 7.66
- 15 -
