Pharmaceutical compositions useful for effecting diuresis and saluresis and for treating hypertension in humans and animals are produced by combining a pyrazol-5-one of the formula: ##STR1## or a pharmaceutically acceptable nontoxic salt thereof wherein R is hydrogen, lower alkyl or amino; PA0 X is methylene, ethylene, methylene wherein 1 hydrogen atom is substituted by lower alkyl, or ethylene wherein 1 hydrogen atom is substituted by lower alkyl or 1 hydrogen atom on each of the two carbon atoms is substituted by lower alkyl; PA0 Y is a direct bond, oxygen or sulphur, provided that when X is methylene wherein 1 hydrogen atom is substituted by alkyl of 1 to 4 carbon atoms, Y is a direct bond; PA0 Z is aryl of 6 to 10 carbon atoms unsubstituted or substituted by: PA1 (a) 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, and alkenoxy of 2 to 4 carbon atoms; PA1 (b) lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl,lower alkylsulphamyl, dilower alkylsulphamyl, --SO.sub.n --lower alkyl wherein n is 0, 1 or 2, or said dialkylamino, carbamoyl, alkylcarbamoyl, dialklycarbamoyl, sulphamyl, alkylsulphamyl, or dialkylsulphamyl, the nitrogen atom of which is a member of a 5-, 6- or 7-membered ring or said ring which additionally contains an oxygen atom; PA1 (c) lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl, lower alkylsulphamyl, dilower alkylsulphamyl, or --SO.sub.n --lower alkyl wherein n is 0, 1 or 2, and 1 or 2 substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkenoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl; or PA1 (d) a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said ring additionally containing 1 or 2 oxygen or sulphur atoms, in combination with a pharmaceutically acceptable nontoxic inert diluent or carrier. The compositions are preferably administered orally or parenterally and in the latter case, sterile or isotonic aqueous solutions are preferred.

The present invention relates to pharmaceutical compositions which are 
useful for effecting diuresis and saluresis in humans and animals and for 
treating hypertension in humans and animals. These compositions are 
characterized by the use of pyrazol-5-ones or pharmaceutically acceptable 
nontoxic salts thereof as the active agent. 
3-Aminopyrazolones have been used as color couplers for color photography 
(A. Weissberger et al. J. Amer. Chem. Soc. 64, 2133 (1942), and as 
intermediates for the preparation of color couplers (British Pat. No. 
599,919; U.S. Pat. No. 2,367,523; U.S. Pat. No. 2,376,380; U.S. Pat. No. 
2,511,231; U.S. Pat. No. 2,600,788; U.S. Pat. No. 2,619,419; U.S. Pat. No. 
2,672,417). 
Pyrazol-5-one derivatives are used as antipyretics, analgesics and 
antiphlogistics (cf. G. Ehrhart and H. Ruschig, "Arzneimittel", Vol. 1, p. 
148 (1972)). 
However, no diuretic, saluretic or antihypertensive activity is known for 
pyrazol-5-one derivatives. 
It has now been discovered that pharmaceutical compositions can be prepared 
for use as diuretics, saluretics and antihypertensives by combining a 
pyrazol-5-one or pharmaceutically acceptable nontoxic salt thereof as 
hereinafter defined with a pharmaceutically acceptable nontoxic inert 
diluent or carrier. 
The present invention also comprises administering to humans or animals in 
need of diuretic, saluretic or antihypertensive therapy, pyrazol-5-ones or 
pharmaceutically acceptable nontoxic salts thereof as hereinafter defined. 
More particularly, the present invention comprises a pharmaceutical 
composition which comprises a diuretic, saluretic or antihypertensive 
amount of a pyrazol-5-one of the formula: 
##STR2## 
or a pharmaceutically acceptable nontoxic salt thereof wherein R is 
hydrogen, lower alkyl especially alkyl of 1 to 4 carbon atoms, or amino; 
X is methylene, ethylene, methylene wherein 1 hydrogen atom is substituted 
by lower alkyl, or ethylene wherein 1 hydrogen atom is substituted by 
lower alkyl or 1 hydrogen atom on each of the two carbon atoms is 
substituted by lower alkyl; 
Y is a direct bond, oxygen or sulphur, provided that when X is methylene 
wherein 1 hydrogen atom is substituted by alkyl of 1 to 4 carbon atoms, Y 
is a direct bond; and 
Z is aryl especially aryl of 6 to 10 carbon atoms unsubstituted or 
substituted by: 
(a) 1 or 2 of the same or different substituents selected from the group 
consisting of halogen, trifluoromethyl, lower alkyl especially alkyl of 1 
to 4 carbon atoms, lower alkenyl especially alkenyl of 2 to 4 carbon 
atoms, lower alkoxy especially alkoxy of 1 to 4 carbon atoms, and lower 
alkenoxy especially alkenoxy of 2 to 4 carbon atoms; 
(b) lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, 
carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl, lower 
alkylsulphamyl, dilower alkylsulphamyl, --SO.sub.n --lower alkyl wherein n 
is 0, 1 or 2, or said dialkylamino, carbamoyl, alkylcarbamoyl, 
dialkylcarbamoyl, sulphamyl, alkylsulphamyl, or dialkylsulphamyl, the 
nitrogen atom of which is a member of a 5-, 6- or 7-membered ring or said 
ring which additionally contains an oxygen atom; 
(c) lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, 
carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl, lower 
alkylsulphamyl, dilower alkylsulphamyl, --SO.sub.n --lower alkyl wherein n 
is 0, 1 or 2, or said dialkylamino, carbamoyl, alkylcarbamoyl, 
dialkylcarbamoyl, sulphamyl, alkylsulphamyl, or dialkylsulphamyl, the 
nitrogen atom of which is a member of a 5-, 6- or 7-membered ring or said 
ring which additionally contains an oxygen atom, and 1 or 2 substituents 
selected from the group consisting of lower alkyl especially alkyl of 1 to 
4 carbon atoms, lower alkenyl especially alkenyl of 2 to 4 carbon atoms, 
lower alkoxy especially alkoxy of 1 to 4 carbon atoms, lower alkenoxy 
especially alkenoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl; 
or 
(d) a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said 
ring additionally containing 1 or 2 oxygen or sulphur atoms, 
in combination with a pharmaceutically acceptable nontoxic inert diluent or 
carrier. 
As used herein the expression "compounds of the present invention" means 
both the pyrazol-5-ones of formula I above and their pharmaceutically 
acceptable nontoxic salts. 
The phrase "lower alkyl", "lower alkenyl", "lower alkoxy" and "lower 
alkenoxy" include both straight and branched chain moieties. 
The compounds according to the present invention exist not only in the form 
shown in formula I but also in the following tautomeric forms: 
##STR3## 
Specifically, the 3-aminopyrazol-5-ones may, additionally, occur in the 
forms I (c) and I (d): 
##STR4## 
The present invention includes the use of the pyrazol-5-ones and their 
pharmaceutically acceptable nontoxic salts in any of the tautomeric forms 
in which they exist. 
In addition, when X in formula I contains an asymmetric carbon atom, the 
compound exists as a racemate and can be resolved into its antipodes. The 
compositions of the present invention must include the pyrazol-5-ones and 
pharmaceutically acceptable nontoxic salts thereof in the form of the 
optical isomers as well as the racemates. 
According to one embodiment of the present invention: 
R is hydrogen, alkyl of 1 to 4 carbon atoms, or amino; and 
Z is phenyl, or naphthyl unsubstituted or substituted by 
(a) 1 or 2 of the same or different substituents selected from the group 
consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, 
alkenyl of 2 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, and 
alkenoxy of 2 to 4 carbon atoms; 
(b) alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms 
in each alkyl moiety, trifluoromethoxy, nitro, cyano, carbamoyl, 
alkylcarbamoyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylcarbamoyl of 1 to 4 carbon atoms in each alkyl moiety, sulphamyl, 
alkylsulphamyl of 1 to 4 carbon atoms, dialkylsulphamyl of 1 to 4 carbon 
atoms in each alkyl moiety, or --SO.sub.n --alkyl of 1 to 4 carbon atoms 
wherein n is 0, 1 or 1; 
(c) alkylamino of 1 to 4 carbon atoms, dialkylamino of 1 to 4 carbon atoms 
in each alkyl moiety, trifluoromethoxy, nitro, cyano, carbamoyl, 
alkylcarbamoyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylcarbamoyl of 1 to 4 carbon atoms in each alkyl moiety, sulphamyl, 
alkylsulphamyl of 1 to 4 carbon atoms, dialkylsulphamyl of 1 to 4 carbon 
atoms in each alkyl moiety, SO.sub.n -alkyl of 1 to 4 carbon atoms wherein 
n is 0, 1 or 2, and 1 or 2 substituents selected from the group consisting 
of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 
1 to 4 carbon atoms, alkenoxy of 2 to 4 carbon atoms, halogen and 
trifluoromethyl; or 
(d) a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said 
ring additionally containing 1 or 2 oxygen or sulphur atoms. 
According to another embodiment of the present invention: 
R is hydrogen, alkyl of 1 to 4 carbon atoms, or amino; 
X is methylene 1 hydrogen atom of which is substituted by alkyl of 1 to 4 
carbon atoms, or ethylene 1 hydrogen atom of which is substituted by 
methyl or ethyl or 1 hydrogen atom of each of the two carbon atoms of 
which is substituted by methyl or ethyl; 
Z is phenyl, or naphthyl substituted by: 
(a) 1 or 2 of the same or different substituents selected from the group 
consisting of alkyl of 1 to 8 carbon atoms, and alkenyl of 1 to 8 carbon 
atoms; 
(b) 1 or 2 of the same or different substituents selected from the group 
consisting of alkoxy of 1 to 6 carbon atoms, and alkenoxy of 2 to 6 carbon 
atoms; 
(c) cycloalkyl of 5, 6 or 7 carbon atoms, or cycloalkenyl of 5, 6 or 7 
carbon atoms; 
(d) 1 or 2 trifluoromethyl moieties; 
(e) trifluoromethoxy, nitro or cyano; 
(f) dialkylamino of 1 to 4 carbon atoms in each alkyl moiety, carbamoyl, 
alkylcarbamoyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylcarbamoyl of 1 to 4 carbon atoms in each alkyl moiety, sulphamyl, 
alkylsulphamyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylsulphamyl of 1 to 4 carbon atoms in each alkyl moiety, or said 
alkylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulphamyl, 
alkylsulphamyl or dialkylsulphamyl, the nitrogen atom of which is a member 
of a 5-, 6- or 7-membered ring or said ring additionally containing an 
oxygen atom; 
(g) --SO.sub.n --alkyl of 1 to 4 carbon atoms wherein n is 0, 1 or 2; or 
(h) a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said 
ring which also contains 1 or 2 oxygen atoms or 1 sulphur atom. 
According to another embodiment of the present invention: 
R is hydrogen, alkyl of 1 to 4 carbon atoms, or amino; 
X is methylene 1 hydrogen atom of which is substituted by alkyl of 1 to 4 
carbon atoms, or ethylene 1 hydrogen atom of which is substituted by 
methyl or ethyl or 1 hydrogen atom of each of the two carbon atoms of 
which is substituted by methyl or ethyl; 
Z is phenyl, naphthyl, or phenyl substituted by: 
(a) 1 or 2 of the same or different substituents selected from the group 
consisting of alkyl of 1 to 4 carbon atoms, and alkenyl of 2 to 4 carbon 
atoms; 
(b) 1 or 2 of the same or different substituents selected from the group 
consisting of alkoxy of 1 to 6 carbon atoms, and alkenoxy of 2 to 6 carbon 
atoms; 
(c) cycloalkyl of 5, 6 or 7 carbon atoms, or cycloalkenyl of 5, 6 or 7 
carbon atoms; 
(d) 1 or 2 trifluoromethyl moieties; 
(e) trifluoromethoxy, nitro or cyano; 
(f) dialkylamino of 1 to 4 carbon atoms in each alkyl moiety, carbamoyl, 
alkylcarbamoyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylcarbamoyl of 1 to 4 carbon atoms in each alkyl moiety, sulphamyl, 
alkylsulphamyl of 1 to 4 carbon atoms in the alkyl moiety, 
dialkylsulphamyl of 1 to 4 carbon atoms in each alkyl moiety, or said 
alkylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulphamyl, 
alkylsulphamyl or dialkylsulphamyl, the nitrogen atom of which is a member 
of a 5-, 6- or 7-membered ring or said ring additionally containing an 
oxygen atom; 
(g) --SO.sub.n ---alkyl of 1 to 4 carbon atoms wherein n is 0 or 2; or 
(h) a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said 
ring which also contains 1 or 2 oxygen atoms or 1 sulphur atom. 
According to another embodiment of the present invention: 
R is hydrogen, alkyl of 1 to 4 carbon atoms, or amino; 
X is methylene, methylene 1 hydrogen atom of which is substituted by alkyl 
of 1 to 3 carbon atoms, ethylene, ethylene 1 hydrogen atom of which is 
substituted by alkyl of 1 to 3 carbon atoms, or ethylene wherein 1 
hydrogen atom of each of the two carbon atoms is substituted by alkyl of 1 
to 3 carbon atoms; and 
Z is phenyl, naphthyl, or phenyl substituted by: 
(a) cyclohexyl or phenyl; 
(b) 1 or 2 of the same or different substituents selected from the group 
consisting of fluorine, chlorine, bromine, iodine, alkyl of 1 to 4 carbon 
atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, 
nitro, cyano, dialkylamino of 1 or 2 carbon atoms in each alkyl moiety, 
and sulphamyl; or 
(c) a trimethylene or tetramethylene moiety which forms a 5- or 6-membered 
ring together with two carbon atoms of the phenyl ring. 
According to another embodiment of the present invention: 
R is hydrogen, methyl, ethyl, n-propyl, isopropyl, or n-butyl; 
X is methylene, methylene 1 hydrogen atom of which is substituted by 
methyl, ethyl, or n-propyl, ethylene, ethylene 1 hydrogen atom of which is 
substituted by methyl, ethyl or n-propyl, or ethylene wherein 1 hydrogen 
atom on each of the two carbon atoms is substituted by methyl; 
Y is a direct bond, oxygen or sulphur, provided that when X is methylene, 1 
hydrogen atom of which is substituted by methyl, ethyl, or n-propyl, Y is 
a direct bond; and 
Z is phenyl, naphthyl, or phenyl substituted by alkyl of 1 to 4 carbon 
atoms, alkoxy of 1 or 2 carbon atoms, fluorine, chlorine, bromine, iodine, 
trifluoromethyl, trifluoromethoxy, nitro, cyano, cyclohexyl, phenyl, 
dimethylamino, sulphamyl, dichlorine, chlorine and bromine, chlorine and 
fluorine, chlorine and methyl, chlorine and trifluoromethyl, chlorine and 
sulphamyl, chlorine and trifluoromethyl, fluorine and methyl, 
trifluoromethyl and methyl, dimethyl, or a trimethylene or tetramethylene 
moiety which forms a 5- or 6-membered ring together with two carbon atoms 
of the phenyl ring. 
According to another embodiment of the present invention: 
R is hydrogen, methyl, ethyl, or amino; 
X is methylene 1 hydrogen atom of which is substituted by methyl, ethyl, or 
n-propyl, ethylene, or ethylene 1 hydrogen atom of which is substituted by 
methyl; 
Y is a direct bond, oxygen or sulphur, provided that when X is methylene, 1 
hydrogen atom of which is substituted by methyl, ethyl, or n-propyl, Y is 
a direct bond; and 
Z is phenyl, naphthyl, or phenyl substituted by 1 or 2 of the same or 
different substituents selected from the group consisting of fluorine, 
chlorine, bromine, methyl, ethyl, and trifluoromethyl. 
According to another embodiment of the present invention: 
R is methyl, ethyl, or amino; 
X is methylene 1 hydrogen atom of which is substituted by methyl, ethyl, or 
n-propyl, ethylene, or ethylene 1 hydrogen atom of which is substituted by 
methyl; 
Y is a direct bond, oxygen or sulphur, provided that when X is methylene 1 
hydrogen atom of which is substituted by methyl, ethyl, or n-propyl, Y is 
a direct bond; and 
Z is phenyl, naphthyl, or phenyl substituted by fluorine, chlorine, 
bromine, methyl, trifluoromethyl, dichlorine, dimethyl, chlorine and 
methyl, or methyl and ethyl. 
The pyrazol-5-ones of the present invention may be prepared by reacting a 
hydrazine of the formula II: 
EQU Z--Y--X--NH--NH.sub.2 II 
wherein 
X, Y and Z are as above defined, 
with an acetic acid derivative of the formula III: 
##STR5## 
wherein X.sup.1 is hydroxy, lower alkoxy, aralkoxy preferably comprising a 
monoaryl moiety and a lower alkoxy moiety, amino or lower alkylamino; 
Y.sup.1 is hydrogen, and 
Y.sup.2 is cyano or a moiety of the formula: 
##STR6## 
wherein Y.sup.3 is hydrogen or straight or branched chain alkyl of 1 to 4 
carbon atoms; or 
Y.sup.1 and Y.sup.2 together form the moiety: 
##STR7## 
wherein Y.sup.4 is lower alkoxy, aryloxy preferably monoaryloxy, aralkoxy 
preferably comprising a monoaryl moiety and a lower alkoxy moiety, lower 
alkylmercapto, aralkylmercapto preferably comprising a monoaryl moiety in 
the lower alkyl moiety, or amino, 
either in the presence or the absence of an inert solvent and of a basic or 
acetic catalyst such as an alkali metal hydroxide, carbonate, halogen 
hydracid, sulphuric acid or a sulphonic acid, at a temperature between 
10.degree. C. and 200.degree. C. 
The pyrazol-5-ones of formula I and their pharmaceutically acceptable 
nontoxic salts may be interconverted according to techniques which are per 
se known in the art. 
The racemates according to the present invention may be resolved into their 
optical antipodes: 
(1) According to methods known in the literature (see, e.g. Houben Weyl's 
"Methoden der Organischen Chemie" IV/2, page 509 ff) by interaction of a 
racemic compound used according to the invention with a chiral medium, 
preferably by reaction of the said compound with a derivative of an 
optically active acid (e.g. camphorsulphonic acid, bromo-camphorsulphonic 
acid or quinic acid) or of an optically active base (e.g. brucine, 
morphine or strychnine) to give a mixture of diastereoisomeric reaction 
products. These products can, with the aid of physicochemical methods 
(e.g. fractionation) be separated and prepared pure, and subsequently 
again resolved into their components. or 
(2) By reaction of the optically pure hydrazine of the formula II (which 
can be prepared by methods known from the literature) with an acetic acid 
derivative of the formula III, e.g. 
##STR8## 
The following compounds are representative of those of the present 
invention: 
1-(.alpha.-methylbenzyl)-pyrazol-5-one, 
1-(.alpha.-methyl-3,4-dichlorobenzyl)-pyrazol-5-one, 
1-(.beta.-phenoxyethyl)-pyrazol-5-one, 
1-(.beta.-(3-methylphenylmercapto)-ethyl)-pyrazol-5-one, 
1-(.beta.-phenethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-3-chlorobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-3-bromobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-3-fluorobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-fluorobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-iodobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-trifluoromethylbenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-trifluoromethoxybenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-3-trifluoromethyl-4-methylbenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-3-chloro-4-bromobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-(naphthyl-(2)-ethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-ethyl-4-nitrobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-ethyl-4-cyanobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-n-propyl-2-chloro-4-fluorobenzyl)-pyrazol-5-one, 
3-amino-1-(.beta.-(2-methylphenoxy)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-(2-chlorophenoxy)-ethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-.beta.-phenoxyethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-.beta.-(3-chloro-4-methylphenoxy)-ethyl)-pyrazol- 
5-one, 
3-amino-1-(.beta.-methyl-.beta.-(4-cyclohexylphenoxy)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-(2-nitrophenoxy)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-ethyl-.beta.-(4-isopropylphenoxy)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-methyl-.beta.-(4-methylphenylmercapto)-ethyl)-pyrazol-5-o 
ne, 
3-amino-1-(.beta.-(naphthyl-(2)-mercapto)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-(3,4-trimethylenephenyl)-ethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-(4-chlorophenyl)-ethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.,.beta.-dimethyl-.beta.-phenethyl)-pyrazol-5-one, 
3-amino-1-(.beta.-methyl-.beta.-(3-chloro-4-methylphenyl)-ethyl)pyrazol-5- 
one, 
3-amino-1-(.alpha.-ethyl-.beta.-phenethyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-sulphonamidobenzyl)-pyrazol-5-one, 
3-amino-1-(.alpha.-methyl-4-chloro-3-sulphonamidobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-butylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-trifluoromethyl-4-chlorobenzyl-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-sulphonamidobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-dimethylaminobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3,4-tetramethylenebenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-chlorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-2-chlorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3,5-dichlorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-fluorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-chloro-3-bromobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-fluoro-3-chlorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-methylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-ethylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-chloro-3methylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-fluoro-3-methylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-methyl-5-chlorobenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3,5-dimethylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-chloro-4-trifluoromethylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-methyl-4-trifluoromethylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-methoxybenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-4-ethoxybenzyl)-pyrazol-5-one, 
3-methyl-1-(.alpha.-methyl-3-ethylbenzyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-methyl-.beta.-phenoxyethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-ethyl-.beta.-phenoxyethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-methyl-.beta.-(3-chlorophenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-methyl-.beta.-(4-chlorophenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-n-propyl-.beta.-(3,4-dichlorophenoxy)-ethyl)-pyrazol-5-o 
ne, 
3-methyl-1-(.beta.-(4-trifluoromethoxyphenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-(4-dimethylaminophenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-(4-iodophenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-(3,4-dichlorophenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-(3-chloro-4-methylphenoxy)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-(naphthyl-(2)-mercapto)-ethyl)-pyrazol-5-one, 
3-methyl-1-(.beta.-methyl-.beta.-(3-chlorophenylmercapto-ethyl-pyrazol-5-on 
e, 
3-methyl-1-(.beta.-methyl-.beta.-(4-chlorophenylmercapto)-ethyl)-pyrazol-5- 
one, 
3-methyl-1-(.beta.-methyl-.beta.-(3,4-dichlorophenylmercapto)-ethyl)-pyrazo 
l-5-one, 
3-ethyl-1-(.beta.-ethyl-.beta.-(4-phenylphenoxy)-ethyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-3-methyl-4-chlorobenzyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-3-chloro-4-methylbenzyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-3,4-dichlorobenzyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-4-trifluoromethoxybenzyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-4-methyl-3-trifluoromethylbenzyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.-methyl-4-bromo-3-chlorobenzyl)-pyrazol-5-one, 
3-ethyl-1-(.beta.-phenylmercaptoethyl)-pyrazol-5-one, 
3-ethyl-1-(.alpha.,.beta.-dimethyl-.beta.-phenethyl)-pyrazol-5-one, 
3-isopropyl-1-(.alpha.-methyl-3,4-dichlorobenzyl)-pyrazol-5-one, 
3-n-propyl-1-(.beta.-phenoxyethyl)-pyrazol-5-one, and 
3-n-butyl-1-(.beta.-phenoxyethyl)-pyrazol-5-one. 
The pharmaceutical compositions of the present invention contain a major or 
minor amount e.g. 99.5% to 0.1%, preferably 90% to 0.5% of at least one 
pyrazol-5-one as above defined in combination with a pharmaceutically 
acceptable nontoxic, inert diluent or carrier, the carrier comprising one 
or more solid, semi-solid or liquid diluent, filler and formulation 
adjuvant which is nontoxic, inert and pharmaceutically acceptable. Such 
pharmaceutical compositions re preferably in dosage unit form; i.e. 
physically discrete units containing a predetermined amount of the drug 
corresponding to a fraction or multiple of the dose which is calculated to 
produce the desired therapeutic response. The dosage units can contain 
one, two, three, four or more single doses or alternatively, one-half, 
third or fourth of a single dose. A single dose preferably contains an 
amount sufficient to produce the desired therapeutic effect upon 
administration at one application of one or more dosage units according to 
a predetermined dosage regimen, usually a whole, half, third or quarter of 
the daily dosage administered once, twice, three or four times a day. 
Other therapeutic agents can also be present. 
Although the dosage and dosage regimen must in each case be carefully 
adjusted, utilizing sound professional judgment and considering the age, 
weight and condition of the recipient, the route of administration and the 
nature and gravity of the illness, generally the parenteral dosage will be 
from 0.01 to 50 mg/kg, preferably 0.1 to 10 mg/kg, of body weight per day, 
and the oral dosage will be from 0.1 to 500 mg/kg, preferably 0.5 to 100 
mg/kg, of body weight per day. In some instances a sufficient therapeutic 
effect can be obtained at a lower dose while in others, a larger dose will 
be required. 
Oral administration can be effected utilizing solid and liquid dosage unit 
forms such as powders, tablets, dragees, capsules, granulates, 
suspensions, solutions and the like. 
Powders are prepared by comminuting the compound to a suitable fine size 
and mixing with a similarly comminuted pharmaceutical carrier such as an 
edible carbohydrate as for example starch, lactose, sucrose, glucose or 
mannitol. Sweetening, flavoring, preservative, dispersing and coloring 
agents can also be present. 
Capsules are made by preparing a powder mixture as described above and 
filling formed gelatin sheaths. Glidants and lubricants such as colloidal 
silica, talc, magnesium stearate, calcium stearate or solid polyethylene 
glycol can be added to the powder mixture before the filling operation. A 
disintegrating or solubilizing agent such as agar-agar, calcium carbonate 
or sodium carbonate can also be added to improve the availability of the 
medicament when the capsule is ingested. 
Tablets are formulated for example by preparing a powder mixture, 
granulating or slugging, adding a lubricant and disintegrant and pressing 
into tablets. A powder mixture is prepared by mixing the compound, 
suitably comminuted, with a diluent or base as described above, and 
optionally with a binder such as carboxymethyl, cellulose, an alginate, 
gelatin, or polyvinyl pyrrolidone, a solution retardant such as paraffin, 
a resorption accelerator such as a quaternary salt and/or an absorption 
agent such as bentonite, kaolin or dicalcium phosphate. The powder mixture 
can be granulated by wetting with a binder such as syrup, starch paste, 
acacia mucilage or solutions of cellulosic or polymeric materials and 
forcing through a screen. As an alternative to granulating, the powder 
mixture can be run through the tablet machine and the resulting 
imperfectly formed slugs broken into granules. The granules can be 
lubricated to prevent sticking to the tablet forming dies by means of the 
addition of stearic acid, a stearate salt, talc or mineral oil. The 
lubricated mixture is then compressed into tablets. The medicaments can 
also be combined with free flowing inert carriers and compressed into 
tablets directly without going through the granulating or slugging steps. 
A clear or opaque protective coating consisting of a sealing coat of 
shellac, a coating of sugar or polymeric material and a polish coating of 
wax can be provided. Dyestuffs can be added to these coatings to 
distinguish different unit dosages. 
Oral fluids such as solutions, syrups and elixirs can be prepared in dosage 
unit form so that a given quantity contains a predetermined amount of the 
compound. Syrups can be prepared by dissolving the compound in a suitably 
flavored aqueous sucrose solution while elixirs are prepared through the 
use of a nontoxic alcoholic vehicle. Suspensions can be formulated by 
dispersing the compound in a nontoxic vehicle. Solubilizers and 
emulsifiers such as ethoxylated isostearyl alcohols and polyoxyethylene 
sorbitol esters, preservatives, flavor additives such as peppermint oil or 
saccharin, and the like can also be added. 
Where appropriate, dosage unit formulations for oral administration can be 
microencapsulated. The formulation can also be prepared to prolong or 
sustain the release as for example by coating or embedding particulate 
material in polymers, wax or the like. 
Parenteral administration can be effected utilizing liquid dosage unit 
forms such as sterile solutions and suspensions intended for subcutaneous, 
intramuscular or intravenous injection. These are prepared by suspending 
or dissolving a measured amount of the compound in a nontoxic liquid 
vehicle suitable for injection such as an aqueous or oleaginous medium and 
sterilizing the suspension or solution. Alternatively, a measured amount 
of the compound is placed in a vial and the vial and its contents are 
sterilized and sealed. An accompanying vial or vehicle can be provided for 
mixing prior to administration. Nontoxic salts and salt solutions can be 
added to render the injection isotonic. Stabilizers, preservatives and 
emulsifiers can also be added. 
Rectal administration can be effected utilizing suppositories in which the 
compound is admixed with low melting water soluble or insoluble solids 
such as polyethylene glycol, cocoa butter, higher esters as for example 
myristyl palmitate, or mixtures thereof. 
The preferred daily dose for parenteral administration is 0.5 mg to 5 g., 
especially 5 mg to 1 g., and for oral administration the preferred daily 
dose is 5 mg to 50 g., especially 25 mg to 10 g. of active ingredient. 
While the routes of administration include oral, parenteral (i.e. 
intramuscular, intraperitoneal, and intravenous) and rectal, oral and 
parenteral are particularly preferred. For parenteral administration, it 
is preferred that the solutions and emulsions be sterile and, if 
appropriate, blood-isotonic. 
Examples of oral and parenteral administrable compositions include the 
following: 
(a) Tablets 
200 g of 3-amino-1-(.alpha.-methyl-4-chlorobenzyl)-pyrazol-5-one are ground 
to a powder and mixed with 300 g of lactose and 200 g of potato starch, 
and after being moistened with an aqueous gelatine solution the mixture is 
granulated through a sieve. 
After drying, 60 g of talc and 5 g of sodium laurylsulphate are added. 
About 10,000 tablets each containing 20 mg of active compound are pressed 
from this mixture. 
(b) Ampoules of injectable solution for parenteral use 
20 g of the sodium salt of 
3-methyl-1-(.alpha.-methyl-3-chlorobenzyl)-pyrazol-5-one are dissolved in 
1,000 ml of propylene glycol and the solution is made up to 5,000 ml with 
water. 
This solution is filled under aseptic conditions into sterile ampoules each 
of 5 ml capacity and each containing 20 mg of active compound. 
The compounds used according to the present invention cause, an oral or 
parenteral administration, a strong increase of excretion of water and 
salt and are therefore useful for the treatment of oedematous and 
hypertonic conditions and for flushing out toxic substances. In addition, 
the compounds can be used in the case of acute renal insufficiency. 
To demonstrate the diuretic and saluretic effect of the compounds used 
according to the invention, 
3-methyl-1-(.alpha.-methyl-3,4-dichlorobenzyl)-pyrazol-5-one, described in 
Example 5, was administered to dogs. The remaining compounds show 
comparable properties. 
Diuresis test with dogs 
(a) Method 
Beagle bitches were given, at intervals of 30 minutes, using a probang, 1 
ml/kg body weight of a solution containing 0.4% of NaCl and 0.2 of KCl. 
The test preparation, in 0.5 ml/kg of 0.1% strength tragacanth mucilage, 
was then administered orally and the change in electrolyte excretion in 
the urine was measured by comparison with control groups. The excretion in 
Val/kg could then be calculated from the volume of urine and the measured 
electrolyte concentration. Sodium and potassium were determined by flame 
photometry. 
(b) Results 
The results are shown in Table 1. The renal excretion of sodium and water 
was considerably increased after oral administration of the test 
preparation. The effect was dependent on the dosage. 
TABLE 1 
__________________________________________________________________________ 
Excretion in .mu. equivalents/kg/30 minutes (Na.sup.+ + K.sup.+) and in 
ml/kg/30 minutes (urine) 
Minutes after Total excretion after 
administration 
1-30 
31-60 
61-90 
91-120 
121-150 
151-180 
administration 
__________________________________________________________________________ 
control 
urine 1.1 1.3 1.3 1.4 1.4 0.7 7.2 
Na.sup.+ 
68 79 45 57 51 36 336 
K.sup.+ 
88 88 64 45 42 25 352 
1 mg/kg 
urine 4.5 11.9 4.6 3.9 1.0 0.6 26.5 
administered 
Na.sup.+ 
358 1238 535 428 64 14 2637 
orally K.sup.+ 
170 259 165 212 102 67 975 
3 mg/kg 
urine 10.0 
16.1 9.8 5.0 2.5 2.0 45.4 
administered 
Na.sup.+ 
969 1932 1251 622 283 218 5275 
orally K.sup.+ 
216 259 216 152 119 103 1065 
__________________________________________________________________________ 
Action of 3methyl-1-(methyl-3,4-dichlorobenzyl)-pyrazol-5-one on the rena 
excretion of electrolyte and urine in awake dogs, as a function of time, 
and total effect after 3 hours. (Mean values for groups of 4 animals). 
The effect of other compounds representative of those of the present 
invention is set forth in Table 2. 
TABLE 2 
__________________________________________________________________________ 
Excretion in .mu. equivalents/kg/hour (Na.sup.+ + K.sup.+) and in 
ml/kg/hour (urine) 
Dose Na.sup.+ 
K.sup.+ 
urine 
__________________________________________________________________________ 
Control 140 
152 
2.0 
##STR9## 10 mg/kg administered orally 
395 
297 
3.4 
(Example 19) 
##STR10## 3 mg/kg administered orally 10 mg/kg administered 
orally 472 1050 
185 330 
6.5 14.7 
(Example 1a) 
##STR11## 3 mg/kg administered orally 10 mg/kg administered 
orally 1122 2964 
461 514 
11.8 22.8 
(Example 6) 
##STR12## 3 mg/kg administered orally 
1637 
218 
14.9 
(Example 24) 
##STR13## 3 mg/kg administered orally 
397 
278 
5.7 
(Example 15) 
##STR14## 3 mg/kg administered orally 
1693 
283 
13.6 
(Example 9) 
##STR15## 3 mg/kg administered orally 
1106 
334 
8.7 
(Example 4) 
__________________________________________________________________________

The following non-limitative examples more particularly illustrate the 
present invention. 
EXAMPLE 1 
3-methyl-1-(.alpha.-n-propylbenzyl)-pyrazol-5-one 
##STR16## 
13 g of acetoacetic acid ethyl ester were dissolved in 20 ml of absolute 
ethanol. 16.4 g of .alpha.-n-propylbenzylhydrazine in a little absolute 
ethanol were slowly added to this solution under nitrogen. After the 
exothermic reaction had subsided, the mixture was heated for 2 hours under 
reflux. 
On cooling, the crude product crystallized out and was purified by 
recrystallization from methanol. 
Melting point: 125.degree.-127.degree. C. Yield: 15 g (65% of theory). 
In a manner analogous to that described in Example 1, the compounds set 
forth in Table 3 may be similarly obtained. 
TABLE 3 
__________________________________________________________________________ 
Example Recrystallization 
Melting point, 
No. Structural formula from Yield .degree.C. 
__________________________________________________________________________ 
1a 
##STR17## Ethanol 78% of theory 
167-169 
##STR18## Ethanol 65% of theory 
158-160 
3 
##STR19## Methanol 71% of theory 
144-146 
4 
##STR20## Dimethyl- formamide 
63% of theory 
150-152 
4a 
##STR21## Ethanol 55% of theory 
140-142 
5 
##STR22## Ethanol 77.7% of theory 
143-145 
6 
##STR23## Ethanol 83% of theory 
165-167 
7 
##STR24## Ethanol 60% of theory 
93-95 
8 
##STR25## Methanol 73% of theory 
135-137 
9 
##STR26## Methanol 82% of theory 
133-135 
10 
##STR27## Methanol 65% of theory 
130-132 
11 
##STR28## Ethanol 85% of theory 
83-85 
__________________________________________________________________________ 
EXAMPLE 12 
3-methyl-1-(.beta.-phenethyl)-pyrazol-5-one 
##STR29## 
13.6 g (0.1 mol) of phenethylhydrazine were added under nitrogen to a 
solution of 13 g (0.1 mol) of acetoacetic acid ethyl ester in 20 ml of 
absolute dioxane; during the addition, the temperature rose to 62.degree. 
C. 
After completion of the addition, the reaction mixture was heated for 2 
hours under reflux. 
On cooling, the reaction product crystallized out. It was recrystallized 
from ethanol. 
Melting point: 130.degree.-132.degree. C. Yield: 13.3 g (66% of theory). 
In a manner analogous to that described in Example 12, the compounds set 
forth in Table 4 may be similarly obtained. 
TABLE 4 
__________________________________________________________________________ 
Example Recrystallization 
Melting point, 
No. Structural formula 
from Yield .degree.C. 
__________________________________________________________________________ 
13 
##STR30## Toluene/ether 
55% of theory 
88-90 
14 
##STR31## Methanol 77% of theory 
149-151 
__________________________________________________________________________ 
EXAMPLE 15 
3-ethyl-1-(.alpha.-methylbenzyL)-pyrazol-5-one 
##STR32## 
16.5 g of .alpha.-methylbenzylhydrazine were dissolved in about 30 ml of 
dioxane and the solution was added under nitrogen to a solution of 17.5 g 
of propionylacetoacetic acid ester in dioxane, in the course of which the 
reaction mixture became warm. After heating for 4 hours under reflux, the 
reaction mixture was concentrated. The product crystallized out on 
rubbing. It was recrystallized from methanol. 
Melting point: 114.degree.-116.degree. C. Yield: 9.5 g (60% of theory). 
EXAMPLE 16 
3-ethyl-1-(.beta.-phenoxymethyl)-pyrazol-5-one 
##STR33## 
17.5 g (0.121 mol) of propionylacetoacetic acid ester were added under 
nitrogen to a solution of 18.4 g (0.121 mol) of phenoxyethylhydrazine in 
isopropanol. The reaction temperature rose to 50.degree. C. After 
completion of the initial reaction, the reaction mixture was heated for 3 
hours under reflux. 
The reaction product crystallized overnight from the oil left after 
concentrating the solution. It was recrystallized from a little ethanol. 
Melting point: 85.degree.-87.degree. C. Yield: 12 g (43.2% of theory). 
EXAMPLE 17 
3-amino-1-(.alpha.-methyl-3,4-dichlorobenzyl)-pyrazol-5-one 
##STR34## 
41 g of .alpha.-methyl-3,4-dichlorobenzylhydrazine, dissolved in absolute 
ethanol, were added dropwise under nitrogen gas to a solution of 31.8 g of 
.beta.-amino-.beta.-ethoxyacrylic acid ethyl ester and 1.5 g of 
p-toluenesulphonic acid in 150 ml of ethanol, at room temperature. After 
stirring for two hours and leaving to stand overnight, the reaction 
solution was concentrated to the maximum extent on a rotary evaporator. 
The residue which remained was dissolved in 2 N sodium hydroxide solution. 
Any unreacted starting products or by-products were extracted with ether. 
The aqueous phase was subsequently brought to pH 5 with acetic acid. The 
oil hereupon produced was taken up in methylene chloride and the organic 
phase was dried over Na.sub.2 SO.sub.4. After evaporation of the solvent, 
the reaction product crystallized out. 
It was recrystallized from methanol. 
Melting point: 127.degree.-129.degree. C. Yield: 21 g (38.5% of theory). 
In a manner analogous to that described in Example 17, the compounds set 
forth in Table 5 may be similarly obtained. 
TABLE 5 
__________________________________________________________________________ 
Recrystal- Melting 
lization point, 
No. 
Structural formula 
from Yield 
.degree.C. 
__________________________________________________________________________ 
17a 
##STR35## Methanol 
28% of theory 
86- 88 
17b 
##STR36## Ethanol 
33% of theory 
128- 130 
18 
##STR37## Ethanol 
38% of theory 
170- 172 
__________________________________________________________________________ 
EXAMPLE 19 
3-amino-1-(.beta.-phenethyl)-pyrazol-5-one 
##STR38## 
20.4 g of phenethylhydrazine were added under nitrogen to 23.7 g of 
.beta.-amino-.beta.-ethoxyacrylic acid ethyl ester in 150 ml of 
tetrahydrofuran after a pinch of p-toluenesulfonic acid had been added. 
The reaction mixture was stirred overnight under N.sub.2 at 40.degree. C. 
and then concentrated in vacuo. The oily residue was dissolved in a little 
2 N sodium hydroxide solution. Any starting materials still present, and 
by-products, were extracted from the aqueous phase with ether. 
The aqueous phase was clarified with charcoal, acidified with acetic acid 
(pH 5) and thoroughly shaken with methylene chloride. The methylene 
chloride phase was dried with sodium sulphate and on concentration yielded 
crystalline product which was recrystallized from ethanol. 
Melting point: 162.degree.-164.degree. C. Yield: 14 g (42% of theory). 
In a manner analogous to that described in Example 19, the compounds set 
forth in Table 6 may be similarly obtained. 
TABLE 6 
__________________________________________________________________________ 
Example Recrystallization 
Melting point, 
No. Structural formula from Yield .degree.C. 
__________________________________________________________________________ 
20 
##STR39## Ethanol 71.5% of theory 
77-79 
21 
##STR40## Ethanol 65% of theory 
126-128 
22 
##STR41## Ethanol 69% of theory 
127-129 
__________________________________________________________________________ 
EXAMPLE 23 
3-amino-1-(.beta.-methyl-.beta.-(3-chlorophenoxy)-ethyl)-pyrazol-5-one 
##STR42## 
A mixture of 31.8 g of .beta.-amino-.beta.-ethoxyacrylic acid ethyl ester, 
150 ml of absolute ethanol, 42 g of 
.beta.-methyl-.beta.-(3-chlorophenoxy)-ethylhydrazine and a pinch of 
p-toluenesulphonic acid was stirred overnight under nitrogen at room 
temperature and then concentrated in vacuo. The residue was triturated 
with a little ether. Hereupon, the crude solid crystallized out. It was 
recrystallized from methanol. 
Melting point: 158.degree.-160.degree. C. Yield: 23 g (43% of theory) 
In a manner analogous to that described in Example 23, the compounds set 
forth in Table 7 may be similarly obtained. 
TABLE 7 
__________________________________________________________________________ 
Example Recrystallization 
Yield, % 
Melting point, 
No. Structural formula from of theory 
.degree.C. 
__________________________________________________________________________ 
24 
##STR43## Ethanol 51 130-132 
25 
##STR44## Ethanol 46.5 124-126 
26 
##STR45## Ethanol 54 91-93 
27 
##STR46## Methanol 44 124-126 
28 
##STR47## Methanol 61 149-151 
28e 
##STR48## Methanol 39 133-135 
29 
##STR49## Methanol 55 115-117 
30 
##STR50## Ethanol 51 100-102 
__________________________________________________________________________