SYNTHESIS O F PYRAZOLONES FROM a-KETO AND a-CYAN0 ESTERS1

BY PAUI. E. GXGNON, J E A N L. DOIVIN,? AND ALEX.\NDIIII C H I S H O I ~ ~ I ~

iZRSTI<ACT 1,4-Dimethyl-3-arnino-5-pyrazolone and 4-methyl- and 4-ethyl-3-amino-l-

phenyl-5-pyrazolo~~es were svntliesizetl from a-keto esters and methy!- and phenylhydrazi~~es. 'I'he hydrazones lirst obtained were transformed into pyra- zolones having a carbethoxy group in position 3, which was converted into arl amino group by a Curtius deg rada t i o~~ . 2,4-Dirnetliyl-3-arnino-5-pyrazolone was obtained directly from rnethylhydrazine arid ethyl a-cyanopropionate. A series of 3-in1ino-2-1i1ethyl-5-~).razolones monosubstituted in position 4 k i t h pentyl, hespl, heptyl, and octyl groups and another series disubsti tutedin position 4 with butyl, hesyl, and heptyl groups were also prepared from the corresponding mo11o- a n d disubstituted cyanoacetates and rnethylhydrazine.

The ultraviolet absorption spectra were determined in lleutral and acid rnediurn.

Pyrazolones prepared from ethyl mono- or disubstitutecl c!.anoacetates and h!.cIrazine have been previously reported (4, 6). Phenylhydrazine, semicarbazide, and X-benzoylliydrazine were condensed in the same way to yield corresponding 2-phenyl-, 2-carboxamido-, and 2-benzoyl-5-pyrazolones (1, 2, 4).

The main object of tlie present work was to study the condensation of methyl- h>-drazine and plien).lhydrazine with a-keto and a-cyano esters with a view of better establishing the constitution of pyrazolones.

Ethyl a-ethos).alylpropionate was reacted with methyl- and plienylliydrazine to J-ield tlie corresponding hydrazones which upon heating were transformed into pyrazolones. A Curtius degradation of the 3-carbethoxy groups was made through tlie hydrazides, azides, and urethanes. The hydrolysis of the urethanes yielded the 4-methyl-3-amino-1-substitu ted-5-pyrazolones.

~ l l a ? ~ ~ l s c l i p t received Jzrly 15, 1952. ContriDulio7~ front 16e Depurtnze7~t of Che711islry, Laval Universily, Quebec, Qlre. T h i s paper

ro,rslil~~fes part qf a tl~esis szrbtititled to t l ~ e Gmd~rclte Sclzool, Laval U7ciz'ersity, i n partial fzrlfillnzent cf 111e reqzsire71tents for tlze degree of Doctor of Science.

Defence Research Board, C.A.R.D.E., Vnlcarlier, Qzre. V r a d z r a t e Sllrdent, lzolder of a Sharui?zigan Clzen~icals Limited Resmrcl~ Sclrolarship a?zd

111tt-r rrsrarch assistant under a Natio71al Research Cozincil of Canada Grant i 7 r 1950-51. Holder (!/' ( I Cailc~tEio7i Itldlrslries Li~izited Research Sclrolarsltip in 1951 -52.

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CAGNON EZ' A L . : SPNI 'EIESIS OF PYH.4ZOLONES 903

Ethyl a-ethoxalylbuty-ate was reacted wit11 pllenylhydrazine in the same wa\-, yielding 4-ethj~l-3-amino-1-phenyl-5-pyrazolone.

Ethyl a-cyanopropionate was heated n ~ i t h methylhydrazine and gave 2,4- cli~nethyl-3-amino-5-pyrazolone. The properties of this compound, for instance, its melting point and ultraviolet absorption spectrum, were quite different froln those of 1,4-dinlethyl-3-ami1~0-5-pyrazolone prepared from ethyl a-ethosalylp~-0- pionate ancl ~nethylhyclrazine.

I t is of interest to note that when an ethyl a-substituted-cj.anoacetate is heated with ~nethylhydrazine, a pyrazolone having a s u b s t i t ~ ~ e n t in position 2 and not in position 1 is formed. Methylhydrazine t h ~ ~ s behaves like phenylhyclrazine (4).

I t has been previously reported that when ~ ~ n s u b s t i t ~ ~ t e d ethyl cyanoacetic ester reacted with methylhydrazine (7) ancl phenylhydrazine ( lo) , pyl-azolones having a methyl or phenyl group in position 1 ancl not in position 2 were formed.

H?C CX H?C C - NH2 I

OC I I 1 + HNH + OC

I \ /" + CzHsOH \

OCyHj HXC6Hj N - C G H ~

By treating other ethyl cyanoacetates a-substituted with pentyl, hesyl, heptyl, and octyl groups with methylhydrazine sulphate in the presence oi sodium ethylate, 4-monos~1bstituted-3-imino-2-11~ethyl-5-pyrazolones \vel-e prepared.

With ~nethylhydrazine sulphate under sin~ilar conditions, e t h ~ ~ l cyanoacetates a-disubstituted with butyl, hexyl, and Ileptyl groups yielded 4,4-disubstitutecl-3- imino-2-methyl-5-pyrazolones.

The individual properties and analj.ses of all the pyrazolo~les prepared are given in Tables I ancl 11.

UItravioIet Absorption Spectra The ultraviolet absorption spectra of the pyrazolones were determined in

neutral and acid solution by a method already described (4) and the results ob- tained are summarized in Tables I and I1 ancl Figs. 1 to 5 .

1,4-Di1nethyl-3-amino-5-pyrazolone, in which the positions of tlle nleth!.l

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GdGNON ET AL.: S Y N T H E S I S OF PYRAZOLOXES 907

groups are fixed by the lnetllod used to prepare the cornpo~ind, ma>;esist in five possible tautomeric forms:

FIG. 1. Ultraviolet absorption spectrum of 1,4-dimethyl-3-an1ino-5-pyrazolo11e: in neutral solution, - - - - - - in acid solution.

FIG. 2. Ultra\riolet absorption spectrum of 4-1nethyl-3-an1ino-l-phenyl-5-pyrazolo11e: in neutral solution, - - - - - - in acid solution;

and of 4-ethyl-3-amino-1-phenyl-5-pyrazolone: - . - . - in neutral solution, ....... in acid solution.

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Stenzel sllowed that the substituent in position 4 could determine \\*hether the 3-substiti~e~lt was an amino or irnino group and that 4-alkyl-3-an1ii10-2-meth~~]-l- phenyl-5-pyrazolo~~es were present largely in the amino form (9). I t has also beer1 shown that p).razolones with a lorn absorption maximum a t high wave length probably have a 2:3 double bond (striicture 11) or an iinino group in-position 3 and that those with a high maximun~ a t short wave length probably have the 3:4 ethylenic bond (structure I)(1, 4, 5).

I t was also found that in alkaline solution pyrazolones exist as form I1 1 (3, 4). In neutral and acid solution, however, the structure probably varies according to the substituents.

1,4-Dimethyl-3-an1ino-5-pyrazolone (Fig. 1) has two ultraviolet absorption nlaxin~a in neutral solution, a low one a t long wave length and a higher one a t short wave length. On acidification, the lo\\, one disappears and the high one is shifted to shorter wave length which is indicative of the presence of an ainino group (8). Then, from urhat has previously been said, one inay conclude that it exists as the two forms I and I1 in neutral solution and only as form I in acid medium.

4-Methyl- and 4-ethyl-3-amino-1-phenyl-5-pyrazolones ma), exist in five struc-

FIG. 3. Ultraviolet absorption spectrum of 2,4-dimethyI-3-a111i110-5-pyrazolone: in neutral solution, - - - - - - in acid solution.

FIG. 4. Ultraviolet absorption spectrum of 4-n-hexyl-3-irnii10-2-methyl-5-pyrazoloi1e: - - -- - in neutral sol~~t ion, - - - - - - in acid solution.

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tures, like the 1,4-dimethyl compound. However, comparison of their ultraviolet absorption spectra (Table 11) (Fig. 2) with those of the 4-methj~l- ant1 4-ethy1-3- amino-2-phenyl-5-pyrazolones, already described (4), reveals that they probab1)- have the 3:4 ethylenic bond ( s t r u c t ~ ~ r e I ) in neutral solution. They have a single .high maximum a t short wave length which corresponds almost esactly with that of the 2-phenyl-5-p)lrazolones just mentioned and since these latter compounds must exist with the 3:4 ethylenic structure, the 1-phen)-1 compouncls probabl\- do also. The difference in behaviol- between the 1-pheriyl conlpounds with one maximum and the 1,4-dimethyl co~npound with two masilna may be ascribed to the ability of the phenyl group to nritlldraw electrons from the ring.

2,4-Dimethyl-3-amino-5-pyrazolone (Fig. 3) malr have the following structures:

I< - C==C - NH? R - CH c = N~ R - c---.c = NH I I I I

OC N - CH, HOC k - CH, I I

O\ ,.-cH3 N

\ / N

\ / N

VIII

FIG. 5. Ultraviolet absorption spectrum of 4,4-di-n-hesyl-3-imi110-2-niet1~yl-5-p~razolo11e: - -- i n neutral solution, - - - - - - in acid solution.

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l'yrazolones were pre\~iousl>~ shown to exist in the hyclrox~.l forin (VIII) iI1 alkaline media (4). In neutral solution, 2,4-cliinetl~yl-3-amin0-5-pyrazol~n~ ex- hibited two maxiina in its ultraviolet absorption spectrum, which suggested that the two forms VI and VII were present. On acidification, one maximum disap- peared. The maximum which remained was a high intensity maximum a t short \\lave length. This type of curve has been previously assigned to pyrazolones with a 3.4 ethylenic bond. Since the 2.3 unsaturated con~pound can not exist, the 3:4 unsaturated form must be present and the imino forin (VII), which is known to give the observed low maximum, must be postulatecl as the forin that disappears.

4-i\~Ioi~osubstituted-3-in~ii~o-2-methyl-5-p~razolones (VII ; R = C5H11, C6Hl3, CiHlj, or CeH17) (Fig. 4) are formulated as having an imino group, which con- firins results previously obtainecl (2). The low maximum in the ultraviolet ab- sorption spectrum of these conlpounds suggests that either they have a 2 :3 double bond or an imino group in position 3, but since they cannot have a stable 2:3 double bond, being substituted in position 2, they must have the imino form.

4,4-Disubstitutecl-3-in~ino-2-i~~ethyl-5-p~razolones (Fig. 5) certainly have the follo\ving structure (IX) in neutral or acid solution since no other one is possible.

R

Their single low intensity absorptioil maximum indicates that the imino group is present.

D(fferences and Analogies of the Pyrazolones H close examination of Tables I and 11, where the properties and analyses of

the different pyrazolones prepared are given, readily indicates their differences and analogies.

For instance, 1,4-dimetl~yl-3-ainino-5-p~-razolone and 2,4-cIin1ethyl-3-ainino-S- p).razolone have the melting points 140" to 141°C. and 223" to 224°C. and the intensities of the maxima found a t the same wave length are 3.48 and 3.94 re- spectively in neutral medium and 3.48 and 3.93 a t 2400 A in acid medium. The two pyrazolones both have a double bond between the two carbons 3 and 4.

4-Methyl-3-amino-1-phenyl-5-pyrazolone and 4-ethyl-3-amino-l-phenyl-5- p)-razolone melt a t 137" to 138°C. and 145" to 146°C. and the intensities of the maxima in neutral inedium a t 2520 A are 4.22 and 4.01 respectively whereas in acid solution they are practically equal, being 4.14 and 4.18, at 2500 A. This shows that the 4-methyl and 4-eth~-I radicals have no great influence on the rest of the molecule.

From Table I1 one easily sees that the maxiina are found a t longer wave length,

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CA CIVOIV El' A I-. I SYhil ' l lESIS O f PYR:IZOLONES 0 1 1.

about 2850 a, for the 4-n1onosubstit~~ted-3-imi11o-2-1netl1yl-5-prazoloes than the:- are for the 4,4-disubstituted-3-in~ino-2-methyl-5-pyraz0011es, 2720 A. The intensities of the maxima however do not differ consiclerably.

EXPERI I\~IENTAL"

All the p)-razolones were prepared by treatment of esters with hg,drazine, 1nethylh)-drazine, or phenylhydrazine. Their properties are listed in Tables I and 11.

Most of them were obtained as viscous liquids. Some solidified on standing for some time but since very few could be purified by ordinary methods it was necessary to use chromatography,

The apparatus was a 1 liter cylinder (6 X 45 cm.) with a large corl; fitted with a wire holder for the filter paper strip. Inside the cylinder was a 50 mi. beaker which contained one of the solvents. The filter paper strips were 50 cm. long and 3 cin. wide. The solvents used were petroleum ether (b.p. 65-110°C.) and water. Other solvent pairs such asn-butanol-water and diethyl ether -water were tried, but with no success. One solvent, usually petroleum ether, was placed in the beaker and the other outside it and the system was allowed to remain undis- turbed for about an hour to reach equilibrium. The impure solid material (about 0.02 gm.) was then placed on the filter paper strip, which was suspended with one end in the solvent in the beaker, the material itself being 2 to 5 cm. above the liquid level. The time necessary for purification varied with the materials and the solvents used fro111 four hours to several days. When the separation was complete, the paper was removed from the solvent and allowed to dry. The compound was recovered a t the original point of application, but i~npurities had diffused ~ ~ p w a r d on the paper so that frequently a perfectly white substance with sharp melting point was obtained which could then be recrystallizecl in a normal manner, or could be sublimed. Sublimation when possible was the best method of purifi- cation. I t was carried out under specific conditions of temperature and pressure for each substance.

1 ,~~-Dimetlzyl-3-carbethoxy-5-~yrazolon.e T o methylhydrazine (4.6 gm., 0.1 mole) was added ethyl a-ethoxyalylpro-

pionate (20.2 gm., 0.1 mole). The mixture was heated for one hour a t llO°C., then for two hours a t 170°C. A dark red viscous liquid was obtained. Yield, 14.2 gm. (76%). The liquid was dissolved in a dilute solution of potassiun~ hydroxide (loyo). The solution, after extraction with ether, was acidified with dilute acetic acid (33%). The acidic solution was then extracted with ether. The ethereal solution was dried over anhydrous calcium chloride. The ether was distilled off and a solid material was obtained which was chromatographed. The white solid from the chromatogra~n was subli~ned a t 140°C. (2 mm.) : 1n.p. 150-151°C. Calc. for C&1?o3X?: N, 15.2%. Found: N , 15.3%.

1 ,d-Dimethyl-3-carbethoxyamino-5-pyrazolone T o boiling hydrazine hydrate (1.0 gm., 0.02 mole) was added l,4-dimethyl-3-

carbethox)--5-pyrazolone (3.0 gm., 0.016 mole). The mixture was heated a t 130°C.

*.111 nleifing poi?rts were takelt on n Dennis meltitrg poitzl nppnmlz~s .

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until evolutio~l of vapors ceased. The resiclue was dissolved in concentratecl h!.clro- chloric acid and the solution was coolecl to - 10°C. in an ice-salt bath. A concen- trated solution of sodium nitrite was added until starch-ioclide test paper gave a positive test for nitrite ion. The colcl solution was extracted with ether, and the ethereal extract was dried over anhydrous calcium chloride. The ether was re- moved under reduced pressure leaving a brown viscous liquid (0.7 gm.) whicll was dissolved in alcol~ol. The solution was refluxed for three hours. After the solution had been allowed to stand for several days, a small amount of 1,4- dimethyl-3-carbethoxyamino-5-pyrazolones was obtained : m.p. 250 to 251°C. Yield, 0.3 gm. (loyo). Calc. for CBH1303Nz: N , 21.1%. Found: N, 20.6%.

I ,d-Dimethyl-3-amino-5-pyrazolone

1,4-Dimethyl-3-carbethoxyan~i110-5-pyrazolone (0,4 gm., 0.002 mole) was re- fluxed in dilute socliuln hydroxide (loyo) for 18 hr. On neutralization to pH f with hydrochloric acid, a large volume of inorganic material precipitated. This was removed b}. filtration. The filtrate was acidified with dilute acetic acid (33Yo), extracted with ether, and evaporated to dryness. A yellow residue was obtained which contained much inorganic material. I t was chromatographed. The material on the paper was extracted with alcohol, and on evaporation of the alcohol a solid precipitated: m.p. 140 to 141°C. Calc. for CsH90N3: N, 33.0%. Found: N, 32.870.

4- Methyl-3-carboxylzydrazide-1 -pAenyl-5-pyrazolo?te

4-Methyl-3-carbethoxy-1-phenyl-5-pyrazolone (11) sublimed a t 140°C. (20 mm.): n1.p. 151 to 152OC. (1.8 gm., 0.007 mole) was added to boiling hydrazine hydrate (5 ml., 0.1 mole) in a 50 ml. round-bottom flask. The mixture was re- fluxed for one hour, left in a vacuum desiccator over calcium chloride for 12 hr., and then recrystallized from ethanol. A white crystalline product was obtained. Yield, 1.4 gm. (83y0). This compound was sublimed a t 140 to 150°C. (20 mm.): n1.11. 179 to 180°C. Calc. for CllH1202N4: N, 24.1%. Found: 22.6y0.

4-Methyl-3-carbetlzoxyami?~o-1 -phenyl-5-pyrazolone

4-Methyl-3-carbethoxp-1-phenpl-5-pyrazolone (11) (5 gm., 0.02 mole) was added to hydrazine hydrate (5.5 ml., 0.11 mole). The mixture was heated a t 120°C. until complete solutio~l of the solid was obtained. The solution was then cooled and acidified with acetic acid; a precipitate appeared. An excess of hydro- chloric acid was added to dissolve the precipitate. The acid solution was cooled to O°C. in an ice bath and a concentrated solution of sodium nitrite was added during mechanical stirring. When the diazotization was complete, as shown by the starch-iodide paper test, the solution was extracted with ether. The ethereal solution was washed with water, then with a dilute (lOyo) sodium bicarbonate solution, with water again, and was dried over calcium chloride. The ether was removed under reduced pressure, which cooled the flask and induced crystalliz- ation of a low melting product which deflagrated: m.p. 60 to 6S°C. This product. the azide, was dissolved in absolute ethanol and refluxed on a steam bath. When the evolution of nitrogen was complete, a white solid material separated from the solution: m.p. 242 to 244OC. Yield, 1.5 gm. (28"). The urethane deco~nposed a t

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170°C. (20 lnrn.) b ~ i t a t 170°C. (1 mm.) it was possible to sublime it. Calc. for C13Hlj03N3: N, 16.1y0. Found: N , 16.2y0.

.$-Methyl-3-anzi~zo-1 -phenyl-5-pyrazolone 4-Methyl-3-carbethoxyamino-1-phenyl-5-pyrazolone (10 gm.) was refluxed

with concentrated hydrochloric acid for 30 min., then with dilute (20y0) hydro- chloric acid for six hours. The suspension was allowed to stancl for 18 hr. The solid obtained was unchanged urethane, which was then refluxed with dilute (10%) sodium hydroxide for 18 hr. The reaction proceeded with formation of a dark solution. On completion of the hydrolysis, the alkaline solution was filtered and acidified with dilute (33y0) acetic acid. A brow11 amorphous material pre- cipitated and there was evolution of a gas. The solid was recrystallized from dilute alcohol: m.p. 137 to 138°C. Calc. for CioHiiONR: N, 22.1%. FOLII I~ : N, 21.3y0.

4-Ethyl-3-carbethoxy-1 -phenyl-5-pyrazolone Ethyl a-ethoxalylbutyrate (21 gm., 0.1 mole) (11) was mixed with phenyl-

11)-drazine (11 gm. 0.11 mole) and the mixture was heated on a s t e a ~ n bath for an hour and in an air bath a t 170 t o 190°C. for 90 rnin. The material was dis- solved in alcohol and the solution poured into dilute alkali. The alkaline solution was filtered, some insoluble viscous materials were thus removed, and the filtrate was acidified with acetic acid. The ester precipitated was redissolved in dilute alkali and reprecipitated: m.p. 199 to 200°C. Yield, 6 gm. (21y0). Calc. for Cl3H16N?O3: I\T, 11.29%. Found: N , 10.7y0.

.4-Ethyl-3-carboxyhydrazido-1 -phenyl-5-pyrazolone T o boiling hydrazine hydrate (10 ml., 0.3 mole) was added pure dry 4-ethyl-

3-carbethoxy-1-phenyl-5-pyrazolol~e (6 gm., 0.023 mole). The mixture was heated a t 125°C. for 90 min. At the end of this time, a straw-colored liquid was obtained which quickly solidified on cooling. The product was recrystallized from water: m.p. 144 t o 145°C. Yield, 4.4 gnl. (90y0). Calc. for Cl?H140?N4: N, 22.8y0. Found: N, 22.5%.

/t -Ethyl-3-~arbetJzoxyamino-1 -phenyl-5-pyrazolone 4-Ethyl-3-carbox~~hydrazido-l-phenyl-5-pyrazolone (2 gm., 0.008 mole) was

dissolved in concentrated hydrochloric acid. The clear yellow solution was cooled to 0°C. and a concentrated solution of sodium nitrite was added until starch- iodide paper turned blue when tested with a drop of the solution. A yellow solid that deflagrated violently on heating precipitated: m.p. 53 to 54°C. Yield, 1.5 gm. (72%). The azide obtained (0.9 grn., 0.035 mole) was refluxed with absolute ethanol for an hour. I t dissolved and on further heating a pale yellow solid pre- cipitated. Yield, 0.5 gm. (53y0 based on the azide). The urethane was sublimed a t 200°C. (2 mm.): m.p. 202 to 203°C. Calc. for C14H1703N3: N, 15.3y0. Found: 15.4y0.

./t -Ethyl-3-amino-1 -phenyl-5-pyrazolone 4-Ethyl-3-carbethoxyamino-1-phenyl-5-pyrazolone (0.5 gm., 0.018 mole) was

treated with dilute (loyo) sodium hydroxide and the nlixture was refluxed for two hours, cooled, filtered, and acidified with dilute (33y0) acetic acid. The brown

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precipitate thrown out of solution was purified by crys1:allization irom dilute alcohol: 111.p. 145 to 146OC. Very nearly quantitative yield was obtained from the hydrolysis. Calc. for C11H130N3: N, 20.7y0. Found: N, 2O.6yO.

2,4-Dimethyl-3-amino-5-pyrazolone Ethyl a-cyanopropionate (12.7 gin., 0.1 mole) was added to methylhydrazice

(4.6 gm., 0.1 mole) and the resulting mixture was stirred. Heat was evolved. Tile material was allowed to stand overnight and a precipitate formed. The solid was filtered off and washed with ether. A sticky brown solid was obtained. This solid was chromatographed and a yellow powder was recovered: 1n.p. 215 to 216OC. I t was sublimed a t 200°C. (1 mm.): m.p. 223 to 224OC. Calc. for C5H90X3: ?T, 33.1Yo. Found, N, 33.2y0. 4-AIkyl-3-imino-2-methyl-5-pyrazolone

h4ixtures of ethyl monosubstituted cyanoacetates (0.1 Inole) and n~ethylhydra- zine sulphate (0.1 mole) were added to solutions of sodium (0.3 mole) in absolute ethanol (100 ml.). After the solutions were refluxed for 18 hr., the alcohol was evaporated under reduced pressure and the residues dissolved in water. The so- lutions were extracted with ether to remove inr reacted starting materials, and the aqueous layers were acidified with acetic acid (33%). Viscous liquids separated from the solutions and solidified on long standing over phosphorus pentoxide. These products were chromatographed and the materials from the chromato- grams were further purified by crystallization from dilute alcohol.

The 4-alkyl-3-imino-2-methyl-5-pyrazolones prepared are listed, together with their melting points, analyses, and ultraviolet absorption spectrophotometric data in Table 11. 4,4-Dialkyl-S-imino-2-melhyl-5-pyrazolones

Ethyl dialkyl instead of monoalkyl cyanoacetates were treated with methyl hydrazine sulphate just as indicated for the 4-alkyl-3-imino-2-methyl-5- . .

pyrazolones. The 4,4-disubstituted-3-in1ino-2-methyl-5-pyrazoloi~es obtained are listed to-

gether with their melting points, analyses, and ultraviolet spectrophotoinetric data in Table 11.

REFERENCES 1. GAGNON, P. E., BOIVIN, J . L., and BOIVIN, P. A. Can. J. Chem. 29: 162. 1952, 2. GAGNON, P. E., BOIVIN, J . L., BOIVIN, P. A., and CRAIG, H. NI. Can. J . Chem. 30: 52.1952. 3. GAGNON, P. E., BOIVIN, J. L., and GIGUBRB, J. Can. J . Chenl. 29: 328. 1951. 4. GAGNON, P. E., BOIVIN, J. L., and JONES, R. N. Can. J . Research, B, 27: 190. 1949. 5 . GAGNON, P. E., NOLIN, B., and JONES, R. N. Can. J . Chem. 29: 843. 1951. 6. GAGNON, P. E., S.~V.~RD, I<., GAUDRY, R., and RICAARDSON, E. D. Can. J . Research, B,

55: 28. 1947. 7. GRAHAM, B., PORTER, H. D., and WEISSBERGER, A. J. 4111. Chem. Soc. 71: 983. 1949. 8. JONES, R. K. J . Am. Cheln. Soc. 67: 2127. 1945. 9. STENZEL, H., STAUB, A., SIMON, C., and BAUXANN, W. Helv. Chim. Acts, 33: 1183. 1950.

10. ~VEISSBERGER, It'. and PORTER, H. D. J. Am. Chem. Soc. 64: 2133. 1942. 11. \\..ISLICESUS, I\''. and ARNOLD, E. Ann. 246: 329. 1888.

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