4-AMINO-0-PHTHALIC ACID.
113.5
The following figures are taken from our laboratory note-book, on metabolism. They are expressed in terms of N / IO ammonia; c c . solution t a k e n .
Free h",$ .. ... Gross urea . . . . . Total nitrogen.. .
Specimen A.
S p e c i m e n B.
-.----
2j
0.6j
IO
19.60
IO
20.
jo
I
0.70 19.hj 20.
jo
...
0.60
1 9 . 6 0 43.30 20.60 44.30
.
Specinten C. I .
0.60 ... 9.00 9.0.j 43.20 4 3 . 2 0 33.80 33.7.7 44.30 4 4 . 1 0 35.60 3j.70
My thanks are due to Dr. P. A. Levene and to Dr. G. W. Heimrod for their advice and encouragement in developing this method and to Mr. Wni. W. Crawford for assistance in preparing this paper for publication. ROCKEFELLER INSTITUTE F O R M E D I C A LRESEARCH, NEW Y O R K CITY, A p r i l 20, 1908.
[CONTRIBUTIOSSFROM
THE
HAVEMEYER LABORATORIES OF COLUMBIA USIVERSITY. No. 154.1
4-AMINO-O-PHTHALIC ACID AND SOME OF ITS DERIVATIVES.' DY MARSTON T A Y L O RBOGERT A N D ROEMER R E X R E N S H A W . R e c e i v e d April 23, 1908.
In a previous paper,* the authors described dimethyl 4-aminophthalate and certain of its acyl derivatives. The present article deals with the free acid, its salts, and various other derivatives or experiments not reported in the earlier paper. The literature on the subject of the free 4-amino-o-phthalic acid is meagre and confusing. Miller3 subjected 4-nitrophthalic acid to the action of tin and hydrochloric acid. The reduction proceeded smoothly, no carbon dioxide was evolved, and presumably the double salt of tin chloride and aminophthalate was formed. This double tin salt remained in solution and could not be separated by freezing (differing in this respect from the corresponding 3-aminophthalic compound). When the tin was precipitated from this solution by hydrogen sulphide and the filtrate from the tin sulphide concentrated, only the hydrochloride of m-aminobenzoic acid remained. reduced 4-nitrophthalic acid to the double zinc acetate and aminophthalate by the Bernthsen and Semper method5 but found the yield inferior to that obtained from the 3-nitro acid. These double zinc acetates and aminophthalates can be diazotized direct and thus used for the preparation of other substituted phthalic acids or for direct coupling. Apparently, he did not attempt the isolation of the free aminophthalic acid. Read at the New York meeting of the Society, Dec. 28, 617 (1906). * Ber., 11, 992 (1878);Ann., 208, 223 (1881). Inaug. Dissertat., Heidelberg (1898). Ber., 19, 164 (1886). -
* THISJOURNAL,
28,
1906.
1136
MARS'I'Oh'
T. IVJGISRT
.4XD ROEMICR R. RENSIIAW.
Seidel' reduced 4-nitrophthalic acid to the amino acid by the action of sodium sulphide, but gives no details as to his method. He states that the acid crystallizes from alcohol in needles iiielting above 2 8 0 ° , but says nothing as to its relative stability. Wegscheider and Bondi' obtained the I-methyl ester of 4-aminophthalic acid by reducing the corresponding nitro compound, and describe it as a yellow indefinitely crystalline compound, decomposing in the vicinity of I . + j o , and quite stable to water or hydrochloric acid. The neutral esters of .+-ainiiioplit!ialic acid are easily prepared from the corresponding nitro esters3 and are quite stable. \Ve ha1.e repeated Xiller's work and confirmed his observations. The reduction of 1-nitrophthalic acid with tin and hydrochloric acid proceeds smoothly, without evolution of carbon dioxide, but when the tin is precipitated as sulphide and the acid filtrate concentrated, carbon dioxide gradually escapes and only ut-aminobenzoic acid remains. lye also tried the reduction of the nitro acid by Seidel's method, with sodium sulphide. Some amino acid was fornieti, but its separation and purification proved slow and troublesome. The 4-atninophthalic acid was prepared readily by saponification of its dimethyl ester and also by hydrolysis of its imide. That the product acid was pro\-en by its analysis thus obtained is really 4-aiiii1io~~hthalic and the analysis of its derivatives, by its reconversion into the characteristic dimethyl ester, byypreparation therefrom of 4-chlorphthalic and of trimellitic acids, and 'by its other reactions. The anhydride and several salts were prepared. The imide rvas obtained by reduction of the nitro imide. .Ittempts to produce the ini'cle from the ammoniuni salts or anhydride of the amino acid were unsuccessful. probably because the methods used involved heating to a temperature where deeper-seated changes occurred. lVhen t h e dimethyl ester was heated to high temperatures with concentrated aqueous amnionia, a methylated imide resulted. Experiments were also conducted with the succinamic, phthalamic, ethoxalyl and phenylurarnino derivatixres of the dimethyl ester, and the urea was obtained from the ester and phosgene. Experimental. Preparation of .$-A vi iiio-o-l'iitianlic Ac,id. ( I ) B y Reduction of the iYityo Acid x itii 7'Cin ( o r S'tannou-i Chloride) a d Hydrochloric Acid.---h just stated, our repetition of Xiller's work COIIfirmed his results. N o carbon dioxide is lost during reduction, but on Her., 34, 1 3 , j l ( I g o I ) . .\lotiafsii., 26, 1063 (1905). a Baeyer, f i o . . , IO, 1.4 anti /. p r o k f . ('hcuc. 53, 3; j ( I Kenshaw&o(.. (.i/.
[?I,
(I~Y;).
AIilkr, iiJifi.,11, I I ~ (1S:sj. I lidinger, lSHC,H,!COOCH,)2.-T~~~ CH,. COT grams of the succinamic acid of dimethyl 4-aminophthalate,' HOOCCH, CH,CONHC,H,(COOCH,),, were heated at 2 10-220' for two hours. The resulting brownish melt was extracted with boiling water, the solution treated with bone-black and concentrated. Large needles separated on cooling which, after recrystallization from water, showed a melting point of 153.4' (cor.). Found: N, 5.16 and j.03. Calculated for C,,H,,O,S:N, 4.81.
The compound crystallizes in colorless prisms or needles; soluble in alcohol, benzene, chloroform, boiling water or hot glacial acetic acid ; nearly insoluble in cold water or in cold acetic acid.
Dimethyl 4-Ph2ltalimidophthaZale, C,H,
I
CI,.\RKIC
chloroform, acetone or hot alcohol; very difficultly soluble in boiling water, carbon bisulphide, ether, petroleum ether, dilute acid or alkalies. 1.1' 31I t 1 .% Y S I V ]'I< 5 1'1 1.. 0 R G A R I C I, 4 HO K A T 0 K S , c I) N E I VTiinit CITS. N. Y , . i p r i l , i ( i 0 q .
[ C O S T R I X l . T I O S S I'RO31 TliS C H E 3 I I C . \ L I , . \ X O X . \ T O K \
01'
H,\RY.\RI)CCil.I,EGK]
METHYL ETHYL ISOBUTYL METHANE. 13s
I,.ATIlA\I
CLAKICI:
Received > l a y
;.
i y \
I n continuing the research on the octanes undertaken some time ago in this laboratory.' the synthesis of inethylethyl isobutyl methane, c H3, ,CH -CH, - CH(CH,,),, or 2-4-dimethyl hexane has been acC,H, complished. I n the preparation of this hydrocarbon the two following series of reactions promised a pure product and both were therefore used. First ,Vethod.-From isopropyl acetacetic ester by saponification methyl isobutyl ketone was obtained. This, when treated with ethyl magnesium bromide, yielded z-+methy1-4-hexanol, CH,CH,--C(OH)-CH,CH-CH,.
1
CH, a€:, This carbinol, on transforming into the corresponding iodide and reducing, gave the desired octane. These reactions are herewith summarized : CH,COCH-CO,C,H,, isopropyl acetacetic ester *
I CH(CH3)2 CH,COCH,-CH(CH,),, methylisobutyl ketone m-+ CH,CH,C(OH)-CH,CH(CH,)?, 2-4-methyl-4-hexanol
is~* - t
I
CH3 CH,CH,-C-(I)-CH,CH(CH,),, I
I
CH, CH,CH,-CH-CH,CH(CH,),,
2-4-methyl-4-iodohexane
-
methyl ethyl isobutyl methane or 2-4-di-
CH, methyl hexane. .Second IZlethod.-Secondary butyl alcohol was converted into the corresponding iodide and made to react with sodium acetacetic ester, thus forming ethyl secondary butyl acetacetate, CH,COCHCO,C,H,. CH,CHCH,CH, 1
l~rcliiiiiii:lr>-niilice.
I!L,J ., 40, ,3;:,
