1148
ORGA4NC AiXD BIOLOGICAL.
ON THE REACTIONS OF THE FORMAMIDINE DERIVATIVES. [SECOXII PAPER.] By F. R. DAIXS A N D E. W. BROWN. Received July 29, 1909.
In a previous paper' it has been pointed out that the substituted formamidines show a peculiar reactivity toward compounds containing methylene hydrogen, such as acetoacetic ester, acetylacetone, etc. At a temperature of I I ~ Oor above, the following reaction occurs: RNHCH : NR f H2CXY = RNHCH : CXY RNH,, thus forming the free amine and a substituted aminomethylene derivative. In case the methylene compound contains a carbethoxy group, a secondary reaction may take place, giving a substituted acid amide as follows : RNHCH :CXCOOEt RNH, = EtOH RlrjHCH :CXCONHR. The completeness of this secondary reaction is conditioned largely by the temperature and the nature of the reacting methylene derivative. Thus with malonic ester the amide formation is practically complete, with acetoacetic ester j o to 80 per cent. of the amine reacts with the carbethoxy group, while with cyanacetic ester no amide formation occurs. The ease of the primary reaction, that is, the replacement of the H, of the :CH, by the group : C H N H R , seems to be affected by the positive or negative nature of the molecule. Thus benzyl cyanide and desoxybenzoin react with greater, difficulty than the more negative malonic or acetoacetic ester and the more positive methylpyrazolone fails to combine with diphenylformamidine, while methylphenyl- and diphenylpyrazolone do so with ease. The following paper is a more extended study of this interesting reaction and, while incomplete, is published a t this time owing to the departure of one of the authors. The investigation is being continued in this laboratory and will be extended to other compounds containing methylene hydrogen, such as the isoxolones, etc. :
+
+
+
Formamidines and .!lalonic Ester.-Di-a-naphthylformamidine is easily prepared in good yield by heating molecular quantities of a-naphthylamine and orthoformic ester on the water bath for several hours. The a-naphthalide of ethyl a-naphthalidomethylenemalomate, a-C,,H,NHCH : C(COOEt)CONHC,,H,-a, was formed when 15 g. of the formamidine and I O g. malonic ester were heated at I j o o for three hours. The product \vas purified by washing with cold alcohol and then crystallizing from benzene and glacial acetic acid. It forms yellow needles dificultly soluble in the usual organic solvents and melts a t 1 6 2 ~ . Analysis: Calculated for C,,,H,,O,N,: N , 6.83. Found : N , 6.57, 6 . 6 j Ber., 35, 2496.
REACTIONS OF T H E FORMAMIDINE DERIVATIVES.
1149
Monobromo Derivatizje.-Two granis of the above compound were dissolved in chloroforni and one molecule of bromine added. This was absorbed instantly a n d was followed by a slow evolution of hydrobromic acid. T h e heavy yellow solid t h a t separated was crystallized from glacial acetic acid. It then melted a t 2 2 7 ' and gave results on analysis t h a t showed the formation of a monobromide, C,,H,,O,N,Br. Calculated: N, 5.74. Found: N, 5.99. An analogous result to the formation of a monobromo compound has been noted in the case of ethyl anilidomethylenecyanacetate.' With the expectation of forming the dinaphthalide, the a-naphthalide of ethyl a-naphthalidomethylenenialonate was heated at z z o o with a n excess of a-naphthylamine but the difficultly soluble yellow powder t h a t resulted melted at 2 8 5 O and gave figures on analysis that indicated the formation of di-a-naphthylurea. Di-,8-naphthylformamidine and malonic ester react easily at 150' to give the P-nafihthalide o j ethyl P-nuphthalidomethylenemalonate. This compound, which is only slightly soluble in boiling alcohol, crystallizes from acetic acid in fine yellow needles melting a t 1 7 z O . Analysis: Calculated for C,,H,,O,N,: N, 6.38. Found: X, 6 . 7 2 . Further evidence of the reactivity of the methylene hydrogen is shown by the fact t h a t malonanilide and di-P-naphthylformamidine, when heated, combine with the forma tion of 1-naphthylamine and /3-naphthalidomethyEenemalonanilide, C,,H,NHCH : C(CONHPh),, a compound difficultly soluble in alcohol and acetic acid, crystallizing in light yellow needles, melting at 289O. Analysis: Calculated for C,,H,,O,N,: N, I O . 31. Found : N, 1 0 . 2 2 . The m-toluide of ethyl m-toluidomethylenemalonate from di-m-tolylformamidine and malonic ester is deposited from alcohol in light yellow needles melting a t 95O. Analysis : Calculated for C,,H,,O,N,: N, 8.28. K, 8.20. Found: +Phenetidine and orthoformic ester failed to react at the temperature of the water bath, b u t when heated in a n oil bath a t 140O gave a good yield of methenyldi-ophenetidine, which crystallized from ligroin in white needles melting a t 8 1 ~ .Analysis: Calculated for C,,H,,O,N,: N, 9.85. N, 9.81. Found : The new amidine is easily soluble in alcohol and this solution, when treated with chloroplatinic acid, deposits on evaporation red crystals of the chlorophtinate which melt a t 1 7 8 ~ . Analysis of the salt dried a t I O O O : Calculated for (C,,H,,O,N,),H,PtCl,: P t , 19.94. Found : P t , 19.95. The above amidine and malonic ester give, a t 130°, a product which melts a t I I O O and is moderately soluble in alcohol, from which i t separates in white needles. This proved to be o-ethozyanilide of ethyl-o-ethoxyanilidomethylewmalonate. Analysis: Calculated for C,,H,,O,N,: N, 7.03. Found: N, 7.00. Derivatives of Ethyl Acetoacetate.-Acetoaceto-p-bromanilide is formed when acetol Ber., 35, 2510.
I 150
ORGANIC .4ND BIOLOGICSL.
acetic ester and p-brornaniline are heated a t 13jo for several hours. The oily product, which solidified on standing, was recrystallized from a mixture of ligroin and benzene, in which i t is difficultly soluble. From this solvent or from hot water i t separates in thin leaflets that melt a t 137.5~. Analysis: Calculated for C,,H,,O,NEr: N, 5.47. Found: s,5 . 3 2 , As this melting point, 13;.5O, is practically the same as that of the product obtained by Knorr' by the action of bromine on acetoacetanilide to which is assigned the formula CH,COCHBrC@KHPh, with a melting point of r3Yo, Knorr's compound was made and was found to melt at 137,jo,but a mixture of this with acetoaceto-pbromanilide melted a t I I O, thus showing them to be different substances. Anilidomet~yleneacetoaceto-p-broma,iilide was readily obtained on heating diphenylformamidine and acetoaceto-p-bromanilicle a t I z 5O, It forms fine, slightly yellowish crystals from alcohol, which melt a t 1 5 8 ~ . Analysis: Calculated for C,,H,,O,X,Br: N , 7.80. Found : N,7 . 9 7 . The isomeric P-bronLanilidometh3leneacetc,ucetunilidemelts a t 17 I O. When di-p-bromdiphenylformaniidinem. I j o o , which is easily prepared from +-bromaniline and orthoformic ester at I O O O , and acetoacetic ester are heated a t 125O, the reaction product contains p-bromaniline and a solid moderately soluble in hot alcohol and acetic acid, which crystallizes in white needles melting a t 190°, the fi-bromanilidomethyleneacetonceto-p-bromanilide. Analysis: Calculated for C,,H,,O,N,Br,: X, 6.39. Found : S, 6 . 7 2 . There is also formed the ethyl-p-bromunilidoinetltyleneacetouc~tate, CH,C@C : (CHNHC,H,Br)CO@Et, white needles easily soluble in alcohol and melting a t I o i o . Analysis: Calculated: N , 4.48. Found: K , 4.76, From acetoacetanilide and di-p-tolylformamidine can be obtained p-toluidometlzy2eneacetoacetanilide, white needles, difficultly soluble in hot alcohol, which melt at 1 4 2 ~ .Analysis: Calculated for C,,H,,O,N,: N , 9. jz. Found : N,9.87. Di-+-cumylformamidine and acetoacetic ester give the following, when heated at 125 O : Pseudocumidine; the +-czLmidomethyLneacetoaceto-~-cuirLidide,white crystals Analysis: from glacial acetic acid melting a t 183'. Calculated for C,,H,BO,N,: N , 7.69. Found : N, 7 . 7 8 . EthyZ-~-clcmido?nethy~eneacetou~etete, white clumps, very soluble in alcohol, m. 98O. Analysis: Calculated for C,,H,,O,N,: N,5.09. Found : iu', 5.39. Di-o-anisylformamidine was made by Riiggeberga by heaking the amine and orthoformic ester in a sealed tube a t 1 6 0 ~ . It can be prepared more simply by heating the components in a n oil bath a t 14oO and crystallizing the product from a mixture of The amidina and acetoacetic ester react benzene and ligroin. It then melts at 105'. Ann., 236, 79. a Dissertation, Freiburg, 1904. '
REACTIONS OF THE FORMAMIDINE DERIVATIVES.
1151
a t I j o o to give ethyl-o-methoxyanilidomthylelteacetoacetate, needle-shaped crystals from alcohol, melting a t IIZO. Analysis: Calculated for C,,H,,O,N: N, 5.32. Found: N, 5.40. Under like conditions methenyldi-$-phenetidine and acetoacetic ester yield the ~-ethozyenilidomethyleneace~oaceto-p-ethoxyanilide, fine yellow crystals, easily soluble in alcohol, which melts a t 138'. Analysis: Calculated for C,,H,,O,N,: N, 7.82. Found : N, 7.70. With acetoacetic ester, di-a-naphthylformamidine yields two products. The first, which consists of fine yellow needles, difficultly soluble in hot alcohol, melts a t 167-So and proved to be a-mzphthulidomethyleeneacetoaceto-a-wphthulide.Analysis: Calculated for C,,H,,O,N,: N, 7.37. Found : N, 7.56. The second is ethyl a-naphthalidomethy2eneacetoacetate,a compound which melts a t 92O and is very soluble in alcohol and moderately soluble in ligroin. Analysis: Calculated for C,,H,,O,N: N, 4.94. Found : N, 5.46. When the naphthalide (m. 1 6 7 ~ )was dissolved in chloroform and bromine ( I mol.) added, the halogen was instantly absorbed with the formation of a dibromide which separated as a heavy yellow powder almost insoluble in boiling acetic acid. It melts a t 226'. Analysis: Calculated for C,,H,,O,N,Br,: N, j.18. Found: N, 5 . 2 2 . I n general, the bromine is loosely bound in these methylene derivatives, as is shown by their tendency to form monobromo compounds, and to even lose all of the bromine on recrystallization. This latter happened in an effort to make a bromide from the corresponding m-xylyl derivative. From di-P-naphthylformamidine and acetoacetic ester was obtained ,B-nu$hthalidomethyleneacetoaceto-B-naphthalide, light yellow granules from glacial acetic acid Analysis: melting a t 184'. Calculated for C,,H,,O,N,: N, 7.37. Found : N, 7.50. Ethyl-,B-na$hthalidomethyleneacetoacetate, white clumps from ligroin, very soluble in alcohol, m. 95O. Analysis: Calculated for C,,H,,O,N : N, 4.94. N, 5.09. Found : Derivatives of Ethyl Cyanacetate.-The formamidines and cyanacetic ester react smoothly a t 125O to yield an amine and the aminomethylene derivative. The carbethoxy group remains intact, no secondary reaction occurring a t this temperature. The following compounds have been obtained: Ethyl-y5-cumidomethyle~ecyawcetate, C,H,Me,NHCH : C(CN)COOEt, white needles from acetic acid melting a t 1 9 6 ~ .Analysis: Calculated for C,,H,,N,O,: N, IO.85. Found : N, 1 1 .oo. Ethyl-a-naphthalidomethyEenecyawcetate, slightly yellow needles from alcohol melting at 146~.Analysis:
ORGANIC AND BIOLOGICAL. Calculated for C,,,H,,O,N,: Found :
B,I O . j j . Ti,10.72.
Ethyl-~-naphthalidomethyleizecyanacetate, brownish yellow needles from alcohol which melt a t I j 2 O . Analysis: Calculated for C,,H,,O,S,: N, 10.j j . Found : S , I O . j8. Derivatives o j Benzyl Cyaizide.--m-Toluidomethj,le,zebenzylcyanide,m-C,H,NHCH : C(CN)C,H,, is formed when benzyl cyanide and di-m-tolylformamidine are heated a t 160--Soo. From alcohol or ligroin the new compound crystdlizes in silver-gray leaves t h a t melt a t 126'. Analysis: Calculated for C,,H,,N,: N , 12 .oo. Found : N, 1 2 . 2 6 . Benzyl cyanide and di-,3-naphthylformamidine fail to react a t 160°, but when the temperature is raised to zooo they combine, yielding the free amine and P-naphthalidomethyle~benzylcyanide. The new derivative, which is only slightly soluble in boiling alcohol, was purified by crystallization from glacial acetic acid, from which i t separated in fine yelloiv needles melting a t 1 9 4 ~ . Analysis: Calculated for C,,H,,S, : S , 10.40. Found : 9, 10.69. Di-a-naphthylforniamidine and benzyl cyanide failed to react a t zooo. Desoxybenzoin, which contains the methylene grouping, unites readily a t I j o o cr-i~npizthulidomethylenedesoxybenzoin, with di-a-naphthylformamidine to yield a-CIoH,NHCH : C(C,HJCOC,H, which crystallizes from alcohol in reddish brown needles melting a t 1 6 1 ~ . Analysis: Calculated for C26H190X:N, 4.00. Found : x, 4 . 2 0 . Derivatives of Acetylacetone.--Acetyl acetone reacts easily a t 1 2 . 5 ~with the formamidines to give aminomethylene compounds of the type RNHCH : C(COCH,),, of which the following have been prepared: Analysis: o-Toluidometizyleneacetylacetonc, white needles from ligroin, m. I 24'. Calculated for C,,H,,O,N: N,6 . 4 j . K , 6.47. Found: m-Toluidomethyleiteacetylaceto1zc, white needles, very soluble in alcohol, m. 7 j O . Analysis: Calculated for C,,H,,O,N: N, 6.45. Found : K, 6.36. a-Phenetidylmethyleneacetylucetune,colorless needles from ligroin which melt a t I 15-6O. Analysis: Calculated for C,,H,,O,N: N, 5.70. Found : N , 5.95. n-Naphthalidomethylen~acetylacetone forms bright yellow needles from alcohol, m. 144'. Analysis: Calculated for C,,H,,O,N : N, j . so. Found : N , 5.81. ~-Na~hthaZidomethyZeneacet).lacetone,brownish needles from alcohol, melting a t 1 2 9 ~ .Analysis: Calculated for C,,H,,O,N: S , 5 . j3. Foiind : PI', 5 . 80.
REACTIONS OF THE FORMAMIDINE DERIVATIVES.
11.53
Pyrazololte and Pyrazole Derivatives.-In order to study the limitations of the formamidine reaction, i t was thought of interest to choose a ring compound containing the methylene grouping. Such compounds present themselves in the pyrazolones formed by the action of phenyl hydrazine on acetoacetic and benzoylacetic esters, compounds which are characterized by their tautomeric behavior, of which this reaction illustrates a phase. Experiment soon showed, for instance, that methylphenylpyrazolone and the formamidines react easily and smoothly according to the following reaction : N = C-Me >CH, RN :CHNHR + 1 PhN - CO N = CMe >C = CHNHR RNH,, 1 PhN - CO yielding substituted aminomethylenepyrazolones, which, containing a chromophoric group, are all strongly colored, red or yellow compounds. Additional evidence of the correctness of the above equation is shown by the fact that a secondary product, methenyl-bis-methyphenylpyrazolone, is often formed in the reaction as follows: N = CMe >CH, R N :CHNHR + z I PhN - CO N = CMe CMe = N I >C=C-CH/ 1 2RNH,. PhN - CO H \CO - NPh This is the first instance observed in which both the RNH and the R N : group of the substituted formamidine have been replaced in reacting with the methylene hydrogen and is an additional confirmation of the interesting analogy between orthoformic ester and the formamidines. Thus Claisen has toundl that the methylene derivatives react with orthoformic ester to give alkoxymethylene conipounds of the type XYC : CHOR, which, in turn with amines, yield the amino derivatives, XYC : CHNHR. These latter, as has been shown, are formed directly from the methylene compounds XYCH, and the formamidines. Both orthoformic ester2 and the formamidines unite directly with methylphenylpyrazolone to give methenyl-bis-methylphenylpyrazolone. Additional proof of the correctness of the above aminomethylene structure is shown in the synthesis of pyrazole rather than pyrazolone compounds by the action of phenylhydrazine on anilidomethyleneacetoacetanilide, a reaction that will be discussed later.
+
+
+
+
Methylphenylpyrazolone was heated with diphenylformaniidine a t 1 3 0 - ~ 0 ~ . The reaction mixture contains two products which can be separated by fractional Ann., 197, 16. Ber., 26, 2j31. a Claisen, Ann., 297, 378.
11.54
ORGANIC AND BIOLOGICAL.
crystallization from alcohol and acetic acid. The more soluble compound is I-phenyl3-meth~~1-4-anilidomethylene-~-pyrazoZone. This forms bright yellow needles melting a t 1j4O. It is soluble in concentrated sulphuric acid and is precipitated without change on the addition of water. Analysis: Calculated for C,,H,,ON,: N, 1 5 . 1 6 . Found : s,1 5 . 0 0 . The second product consists of orange-red needles difficultly soluble in alcohol and acetic acid and melts at 18oO, and proved to be methyl-bis-methylphenylpyrazolone. Analysis: Calculated for C2,HI8O2Nt:N, 15.64. Found : N, 1 5 . 6 9 . This latter compound may result from the direct interaction of two molecules of the pyrazolone and one of the formamidine or may be formed in a secondary reaction between methylphenylpyrazolone and the aminomethylene derivative. Thus experiment showed t h a t a quantitative yield of the methenyl-bis-pyrazolone can be obtained by heating methylphenylpyrazolone and ~-naphthalidornethylenen~ethylphenylpyrazolone at 1 5 0 ~ . CloH,O : CHNHCloH7-j CloHloO = /3-CloH7NH, Cj0H8O: CHCloH,O. Under like conditions, methylphenylpyrazolone and di-9-naphthylformamidine yield inethenyl-bis-?nethylpheltylpyrazoloize and 1-phen~1-3-metiiyl-q-~-naphthalidomethylen.e-5-pyrazoloize, yellowish brown needles from alcohol melting at 177". Analysis: Calculated for C,,H,,OK,: N, 1 2 . 8 5 . Found : N, 13.02. The corresponding a-na~hthalidomethylenemethylphenylfiyrazoloneconsists of deep yellow crystals t h a t melt a t 1 2 2 ~ . .4nalysis: Calculated for C,,H,,OK,: N, 12.85. Found : N , 13.28. When boiled with alcoholic potash the pyrazolone yields a red compound melting at 174', which is under investigation. Other pyrazolones are the following: ~ - P h e n y l - ~ - m e t h y l - ~ - p - b r o m a n i l i d o ~ e t h y l e n e - ~ - ~ y r a dark z o l o nbrown e, needles from alcohol, ni. 168'. Analysis: Calculated for C,,H,,ON,Br: N, 1 1 .80. Found : s,1 2 . 2 . 1-Phenyl-3-n~eth~l-4-P-folziidomethyleiie-j-~yrazolone, yellow needles from alcohol, 111. 1 6 4 ~ . Analysis: Calculated for C,,H,,ON,: N, 1 4 . 4 4 . Found : K, 1 4 . 4 6 . ~ - ~ h e l t y l - ~ - m e t h y l - ~ - ~ - c l L m i d o m e t l ~ y l ~ ~ ~ e - yellow ~ - ~ ~ r a needles z o ~ o n e ,from alcohol, m. 171'. Analysis: Calculated for C,,H,,ON,: X , 1 3 . 1 6 . Found : N , 13.09. ~-Phenyl-~-~nefhyl-g-~-etlzoryanilido~nethj~lene-~-pyrazoloite, reddish yellow crystals, m. 162'. Analysis: Calculated for C,,H,,ON,: F,13.09. Found: S , 12.88. Deri-jatives of DiphenyZpyrazolone.-~,~-Diphenylpyrazolone from benzoyl acetic ester and phenylhydrazine reacts easily with the formamidines at 1 2 5 ~ . Thus from the pyra701one and diphenylformamidine was obtained 1,3-diphe.nyl-4-anili~~zethyl-
+
+
REACTIONS OF T H E FORMAMIDINE DERIVATIVES.
1155
ene-5-~y~uzolom.This crystallized from glacial acetic acid in fine yellow needles melting a t 1 4 0 ~ . Analysis: Calculated for C,H,,ON,: Found: Diphenylpyrazolone
and
N, 12.39. N, 12.35.
di-o-tolylformamidine gave
r,jl-di~henyZ-4-o-toZuido-
ntsth.yZelle-j-~yrazoZone, yellow needles from acetic acid melting a t 146". Analysis:
Calculated for C,,H,,ON,: Found:
N, I I. 89. N, 11.72.
Diphenylpyrazolone and di-P-naphthylformamidine yield r,3-di~hen~Z-4-P-1phthaZidomethyZene-~-pyrazolone, yellow crystals, difficultly soluble in glacial acetic acid, m. 1 9 2 ~ . Analysis: Calculated for C,,H,,ON,: N, IO.79. Found : N, 10.73.
Pyrazole Syrzthesis.-Ruggeberg' investigated the action of phenylhydrazine upon anilidomethylenebenzoylacetanilide and 0-toluidomethylenebenzoylacet-o-toluidideand obtained compounds which he regarded as aminome€hylene derivatives of diphenylpyrazolone. The two products, however, fail to agree with the properties of the anilidomethylene- and 0-toluidomethylenediphenylpyrazolone previously described. These melt a t 140' and 146', respectively, while Ruggeberg's compounds have melting points of 1 5 5 ' ~and 160'; For the purpose of more complete identification his work was repeated in the latter case. The 0-toluidomethylenebenzoylacet-o- toluidide was heated for three hours in alcohol solution with phenylhydrazine. After purification there was obtained a compound crystallizing in pure white needles, melting a t 165'. Riiggeberg's product was yellow and melted a t 160'. Analysis, however, showed their identity. Calculated for C,,H,,ON,: N, I I . 89; found, IZ . 0 2 per cent. Further investigation identified this compound as the o-tolyl amide of 5-diphenylpyrazole-4-carboxylicacid and showed that phenylhydrazine reacted with the aminomethylene derivatives of acetoacetic and benzoylacetic esters to give a series of pyrazoles isomeric with the pyrazolones previously described. In the formation of such a ring with phenylhydrazine, three possibilities offer themselves which can be represented as follows: CH,CO
I.
I
RHNHC : CCONHR
HZN
+ HNPh
CH,CO
11.
I
RNHCOC : CHNHR
$.
-
H,N HNPh
CH,C
I
=
N
>NPh RHNHC : C - CO CH,C =
1
=
N
> N P h + RNH, RHNCOC= CH
( r-Phenyl-3-methyl-4-CONHR)
Dissertation, Freiburg, 1904. I ,~-diphenylpyrazole-4-carboxylic acid.
* This is the phenylamide of
+ RNH,
I 156
ORGANIC A N D BIOLOGICAL.
CH,CO 111.
HNPh
!
I~HNCOC : CHNHR
H$
'
CH,C-NPh __ .~
11
>N
RHNCOC---CH
+ RNH,
(~-Plienyl-~-rnetliyl-~-COh"R)
Equation No. I , the pyrazolone synthesis, suggested bv Ruggeberg, is out of the question, since no aminomethylene derivatives are obtained. Against this also is the fact that the COSHR group is unaffected by the phenylhydrazine, Experiment has shown that anilidomethyleneacetoacetanilide and fi-toluidomethyleneacetoacetanilide give, with phenylhydrazine, the same pyrazole with melting point 182') which is only possible when the COSHPh group remains intact. The formation of these pyrazole derivatives must be explained by equation I1 or 111, the question being whether the methyl or phenyl groups are in positions 3 or 5 . The direct evidence thus far obtained points to equation I11 as the correct formulation of the reaction and thus places them as derivatives of 1-phenyl-5-methyl or phenyl-4-carboxylic acid for the following reason. Ethyl ,l~naphthalidomethyIeneacetoacetate was boiled with excess of phenylhydrazine in alcohol solution. After removal of the excess of phenylhydrazine, the resulting product was purified by crystallization from ligroin. I t then melted at 55-6' and when saponified with alcoholic potash gave an acid melting a t 167'. This ester and acid were found to be identical with the ethyl I-phenyl5-methylpyrazole-4-carboxylate and corresponding acid of Claisen,' who made them by the action of phenylhydrazine on oxymethylene acetoacetic ester. The equation which follows, CH,CO
HNC,H,
f
i
CH,C - NC,H, -. -
+
\N C,,H,NH, II Et0,Ck : CHNHC,,H, H,N E t0,CC - CH // shows the mechanism of the reaction, illustrates the analogy between the grouping C : CHOR and C : CHNHR in ease of replacement and gives the proof of the structure. The p h e n y l a m i d e 01 ~ - p h c n j ~ l - ~ - m c t h y l ~ ~ r u ~ o l e - q -lic c a racid h o r ~is formed when anilidomethyleneacetoacetanilide is heated for two hours in alcohol solution with a n excess of phenylhydrazine, The solution was then poured into water acidified with hydrochloric acid. The resulting precipitate was purified by crystallization from d c o hol and benzene, from which i t separates in white crystals melting a t 18zO Analysis: Calculated for C17€I:5ClK3: K, I j . 16. Found : K, 15.14. .4s has been noted, this same pyrazole can be made by the action of phenylhydrazine on p-toluidomethyleneacetoacetanilide. The p-tolylamide o j ~ - p i i e n ~ Z - ~ - n z e ~ h , ~ l p ~ r u z o l c - ~ - c acid u r b ois r ~readily ~ l i c obtained from p-toluidoniethyleneacetoaceto-p-toluide and phenylhydrazine. I t forms white Analysis: needles from alcohol melting a t 177'. Ann., 295, 312
INTRAMOLECULAR REARRANGEMENT OF PHTHALAMIDIC ACIDS.
II57
Calculated for C,,H,,ON,: N, 14.43 Found : N, 14.34. Under like conditions, a-naphthalidomethyleneacetoacet-a-naphthalide gave the a-mphthalide of 1-phenyl-~-methylpyrazole-4-carboxylic acid, white needles from alcohol, melting a t 1 6 8 ~ . Analysis: Calculated for C,,H,,ON,: N , 12.8j. Found : N, 12.88. The P-naphtkalide of 1-phenyl-5-methylpyvazole-q-carboxycylic acid crystallizes from alcohol in white needles which melt a t 1 7 0 ~ . Analysis: Calculated for C,,H,,ON,: K, 12.85. Found : N, 12.91.
These pyrazole derivatives are all colorless compounds with melting points ten to thirty degrees higher than the corresponding isomeric colored pyrazolones. W A S E B U R N COLLEGE, T O P E X A , KANSAS. INTRAMOLECULAR REARRANGEMENT OF PHTHALAMIDIC ACIDS. IV. B Y J.
BISHOP TINGLEA N D B. F. PARLETT BRBNTON. Received August 4, 1909.
The previous papers on this subject by the senior author and his collaborators’ have shown that secondary and tertiary amines, if they are not too negative, convert phthalamidic acids, RNHCOC,H,CO,H, into
co 4\co/\NR,
imides, C H
/
whereas primary amines, R’NH,, give rise to
one or more of the following products: the amidic acid, R’NHCOC,H,CO,H, the
imides,
C H /‘O>R
’
‘\CO
or C H /‘O>R/,
’
or
the
amides,
‘\CO
RNHCOC,H,CONHR’ and C,H,(CONHR’),. In all cases, of course, the primary product of the reaction is an ammonium salt. In the present communication we describe the results which we have obtained by a more extended study of the above reaction. On account of the rather curious and unexpected observations described by Bishop Tingle and Rolker,, our attention was first directed towards the behavior of ph thal-m-nitrophenylamidic acid, OZNC,H,NHCOC,H4CO2H, and we have investigated its interaction with a considerable number of amines of various classes. We obtained normal salts from butylamine, isobutylamine, isoamylamine, benzylamine, benzyle thylamine and dibenzylamine; all of these salts, when heated above their melting points, evolved the amine and gave phthal-m-nitrophenylimide. With ammonia, diBishop Tingle and Cram, Am. Chem. I., 37, 596 (1907); Bishop Tingle and Lovelace, Ibid., 38, 642 (1907) ; Bishop Tingle and Rolker, THISJOURNAL, 30, 1882 (1908). LOC. Cit.
’
