729
QUINAZOLINES
.................................................. ...............................................
K NH,
................................................ ................................................ 2 H,O ...............................................
Found
Calculated
3.85 9.79 8.43 17.96 9.94
4.22 9.72 7.87 18.06 9.70
Experiment indicates that cadmium’ forms compounds of a similar composition. T h e investigation of these products is being continued in this laboratory. W A S H B U R N COLLEGE,
Topeka, Kan., Feb. 16, 1907.
HAVEMEYER LABORATORIES O F COLUMBIA UNIVERSITY, No. 132.1
[COXTRIBUTIONS FRO31 THE
RESEARCHES ON QUINAZOLINES (19TH PAPER). THE SYNTHESIS OF 1,3,6,8-NAPHTHOTETRAZINESFROM PARADIAMINOTEREPHTHALIC ACID AND FROM CERTAIN OF ITS DERIVATIVES.2 BY MARSTON TAYLOR BOGERTA S D JOHN MAURICENELSON. Received February 9, 1907.
Bogert and Dox prepared two naphthotetrazines from ethyl succinylosuccinate, one by condensation with guanidine3, the other by condensation with acetamidine*. Their attempts to obtain similar compounds from #-diaminoterephthalic acid resulted unsuccessfully. T h e authors of the present paper, as the result of further experimenting in this direction, have now succeeded in accomplishing this synthesis, and have prepared and studied several naphthotetrazines from p-diaminoterephthalic compounds. T h e experiments may be briefly summarized as follows:W h e n ethyl #-diaminoterephthalate is treated with phenyl isocyanate, ethyl diphenyluraniinoterephthalate results. By the action of acetic anhydride upon this phenyluramino ester, ethyl s-diacetyldiaminoterephthalate, and tetracetyldiaminoterephthalate are formed, according to the following equations : ROOC,
C,H,NHCONH/
N H C O N H C,H,
C6Hz< c0OR
< >
NHCOCH,
C,H,
COOR
CH,CONH
ROOC C,H,NHCONH
+ (CH,CO),O
+ C,H,NHCOCH, + CO,,
NHCO NC,H,
‘‘HZ latioti may be converted into diacetj 1 derivatives through the phenyluramino compound. W e shall test this question later, as time permits. From P-dianiinoterephthalic acid and acetic anhydride, the di-acetanthranil (di-lactam of s-diacetyl-#-dianiinoterephthalic acid) was obtained: OC\/\/SCOCH, I
N
CH,COS/\/\CO Naphthotetrazines were prepared by heating ethyl $-dianiinoterephthalate with formamide I , by heating its acetyl derivative with primary amines', by the action of primary amines upon the above di-acetanthranil,, and by heating the diphenyluraminoterephthalic ester with aniline ; the reactions involved being as follows : I.
/\
ROOC
v
,
I
H,N
KH2
\/ HCONH,=
-
A\//\ COOR
ROOC\//\ySHCOH I
HCONH
/\
H'XCO
\/ /\
\/
\/ I
I I
I HCONH
/\
/\
\/
--
2NH,
-,-
zROH =
COOR NHCOH
A CONH,
'Niementowski, J. pr. Chem., 51,,564(1895);Bogert and Chambers, This Journal, 27, 650 (1905). ' Weddige, J. pr. Chem., 36, 141 (1887) ; Zacharias, Ibid., 43,432 (1891); Thieme, Ibid., 43, 451 (1891). Anschutz, Schmidt a n d Greiffenberg, Ber., 35, 3840 (1902);Bogert and Chambers, This Journal, 27, 649 (1905),28, 207 (1906);Bogert and Seil, Ibid., 27, 1305 (I905),28, 884 (1906).
QUINAZOLINES
731
OH I C
A ”/ \,/ \/
co
i
1
-
N
1
d
I
A
// \,/ , \/
N
\CH
\CH
1 +zROH
I
l
CH
N
co
N
ROOC,,
,NHCOCH,
\/
c i
+zH,O,
OH 11.
/
””“>
\COOR /NHCOCH,
CH,CONH
\CONHR, / N = CCH, \CO--NR,1
z=
+ zR’XH, = $- z R O H =
R’y-co)
CH,-C 111.
C6H2’
CH,CONH
N
‘>
H‘,Z
oc CH,CON
NCOCH, H ‘, Z
(do
+ zR‘NH, =
/NHCOCH, CH ,C0N H R’N-CO
\
CH,!! = N/
(cooR
( $C6H,NH2)
+
=
I c6H,(NH-70 zROH. CO-NH CO - NC,H, By these various reactions, the following naphthotetrazines were prepared : 4, g-diketotetrahydro- I , 3,6,8-naphthotetrazine (4, g-dihydroxyI ,3,6,8-naphthotetrazine) , the n,7-dimethyl derivative of the latter, ~,7-dimethyl-3,8-diisoamyl-4, g- diketotetrahydro-I ,3,6,8-naphthotetrazine (and the corresponding intermediate amide), 2,7-dimethyl-3,&diphenyl4, g-diketotetrahydro- I , 3,6,8-naphthotetrazine, and 3,8-diphenyl-n,4,7,gtetraketooctahydro- I, 3,6,g-naphthotetrazine( 3,8-diphenyl-z,7-dihydroxy4,g-diketotetrahydro-1,3,6,8-naphthotetrazine). Most of these substances melt very high or are infusible. They are insoluble or very difficultly soluble in the usual organic solvents. T h e isoamyl compound, however, melts relatively low (179’ corr.), and can be crystallized from
732
XI. T. BOGERT A S D J . n1. NELSON
alcohol. We have pointed out elsewhere that in the ~-quinazolonesas the molecular weight of the alkyl increases the melting point falls, and it is not unlikely that the same will be found to be the case with these naphthotetrazines. Of the naphthotetrazines investigated so far, those contaiiiing the group -COSH-C(OH):S- dissolve readily in dilute caustic alkalies, and are re-precipitated from such solutiolis by dilute acids or by carbon dioxide. Ethyl diacetiniinoiuccinylosuccinate was also prepared and some experim5nts conducted with it, but the acyl derivatives in this series are very much less stable, and we have not been able to obtain any heterocyclic condensations from them. T h e work upon diaminoplithalic acids, succinylosucci~~ic acid, and the naphthotetrazines is being continued. Experimental. The Preparation of P-Diaiitiizoterep~flalicAcid was carried out as described by Bogert and DOX', by converting ethyl succinylosuccinate into its diimine, oxidizing this Lo ethyl dianiinoterephthalate, and saponifying tlie latter. 111 tlie oxidation of the diimine to the diamiiio ester by the action of bromine and sulphuric acid, the observation was made that the diimine must be added to the acid and not the acid to the diiniine. If the latter order is followed, sufficient heat is generated to destroy much of the diimine, unless recourse is had to external cooling. Ethyl Diph my luya Ininotere) tha la te , ( 2 ) C,H,NHCOXH COOC,H, ( 4 ) --Three grams (one C&* / ( I ) C,H,OCO \SHCOSHC,H, (5) molecule) of ethyl diaminoterephthalate were dissolved i n 60 cc. of dry benzene in a flask provided with a return condenser and placed on the steam bath, and 2.83 grams (two molecules) of phenyl isocyanate added to the clear solution (excess of phenyl isocyanate appears to be without effect upon the result). After warming for a few minutes, the phenyluramino derivative began to separate as a light yellow precipitate, and in about fifteen minutes the reaction was complete, the yield being practically theoretical. T h e precipitate was filtered off, washed with dry benzene, recrystallized from nitrobenzene, washed well with hot alcohol, dried a t I 10' to constant weight, and analyzed with the following results : F o u n d : C, 63.22;H, 5 - 2 4 ; N 11.19. Calculated for C,,H,,O,N,: C, 63.93;H , 4.91;N, 11.47. On account of the insolubility of this suhstance, it is difficult to thoroughly purify it, and this is the cause of the somewhat wide variation of the percentages found from those calculated.
z.
>
This Journal, 27, 1136(1905).
QUINAZOLINES
733
The pure phenyluramino compound is a light yellow, crystalline solid, melting with decomposition a t about 262'. It is very difficultly soluble in water, alcohol, carbon tetrachloride, ethyl acetate, amyl valerate, or benzene, but may be crystallized from nitrobenzene. Acetic anhydride gradually dissolves it with formation of acetyl derivatives of ethyl diaminoterephthalate. \Vhen the phenyluramino ester was boiled with a freshly prepared alcoholic solution of sodium ethylate, a yellow sodium salt separated, which was dissolved in water and the solution precipitated by adding acetic acid. T h i s precipitate may be the free phenyl uramino acid COOH C,H, N H CO N H , but not enough was obtained HOOC
