[CONTRIBUTION FROM
THE
CHEMICAL LABORATORY OF TRINITY COLLEGE ]
T H E COSDEKSATIOS OF AJlINOAXTIPYRISE. T’. A COMPARISOS OF AATISOAXTIPYRINE WITH p-AMISODIT\.’IETHYLANILISE, p-PHEXYLEXEDIAMISE, ,4SD p-AILII?;OPHEKOL (1)l E. EMERSOS, K. KELLY, H . BEACHAM,
AND
L. BEEGLE
Received January 21, 1944
In previous articles it was reported (2) that aininoantipyrine reacted with phenols and phenolic compounds in an alkaline oxidizing medium to form colored solutions from which the colored compounds could be isolated. It was noted that this reaction was similar to that of phenolic compounds with p-diamines and p-aminophenols. The determination of the usefulness of aminoantipyrine as a reagent for phenols was made by comparison with p-aminodimethylaniline, p-phenylenediamine, and p-aminophenol under similar conditions. The tests were carried out in solutions of the phenols having a concentration of 1:10000. Potassium ferricyanide was used as an oxidant2 and each test was made in the presence of four alkalizing agents, sodium bicarbonate, sodium carbonate, ammonium hydroxide, and sodium hydroxide. The results are shown in Tables I and 11. Some of the coupling amines form colored solutions with the oxidant in the absence of phenols and, in order for one to interpret the results of the color tests, controls are necessary. Table 111 shows the color of the controls. I n many cases, especially when the concentration of the phenol is low and the color indicative of a positive test is not transferable to the chloroform layer, a positive reaction is obscured by the colored oxidation products of the coupling amine. This situation occurs particularly with p-aminodimethylaniline and p-phenylenediamine. DISCWSION
A. The coupling amines. 1. The intensity of the color in the test solutions and the number of positive tests produced with the amines place them in the following order of decreasing sensitivity : p-aminodimethylaniline, aminoantipyrine, p-phenylenediamine, p-aminophenol. 2. The tests obtained with p-aminophenol and p-phenylenediamine are often 1 Taken from part of the work submitted by K. K., H. B., and L. B. to the graduate faculty of Trinity College in partial fulfillment of the requirements for the degree of hfaster of Science. The following oxidizing agents were tried in some of the tests: *4mmonium persulfate, ammoniacal cupric sulfate, ammoniacal silver nitrate, ammoniacal silver chloride, hydrogen peroxide, potassium chlorate, sodium hypochlorite, sodium nitrite, sodium perborate, potassium permanganate, mercuric chloride, and ceric ammonium sulfate. The persulfate is superior t o the other compounds and in some respects better than potassium ferricyanide because i t imparts no color of its own to the test solutions. The reaction is slow and where the colored product formed is unstable i t may be destroyed almost as rapidly as i t forms. Where i t is known that the colored product is relatively stable i t is suggested that persulfates be used in developing the reaction colorimetrically. 226
CONDENSATION O F AMINOAI\;TIPYRINE
227
difficult to evaluate due t o the development of turbid solutions or solutions having nondescript colors. This is especially true of p-phenylenediamine. Sometimes these solutions produce chloroform layers having well-defined colors, but frequently this is not the case and the results are uncertain. This disadvantage is not found with paminodimethylaniline or aminoantipyrine. 3. Solutions of the coupling amines, with the exception of aminoantipyrine, decompose to form highly colored solutions and precipitates after short standing. 4. In order to be sure of the color of the solutions the tests were made in daylight rather than in ordinary artificial light. However, the results of tests in which aminoantipyrine is used can be interpreted ryith equal ease in day or artificial light. 5 . The compounds listed in Table I1 all have substituents in what is believed to be the coupling position and a positive test with them is thought to take place with expulsion of these substituents. With these compounds the reaction with the coupling amines is aminoantipyrine > p-aminodimethylaniline > p phenylenediamine > p-aminophenol. 6. In a previous paper (3) it was noted that if a color reaction took place with arnjnoantipyrine the color lvould be green or blue if only two tautomeric forms are poseible in the coupling ring of the phenol and red if three or more forms are possible. This great difference in the depth of color is not observed with the other coupling amines. Where it is possible for one to obtain information relating t o the structure of the phenolic compound by means of color tests, aminoantipyrine has been found to be a better reagent. B. The alkalies. 1. I n general, sodium bicarbonate is the best alkalizing agent and sodium hydroxide the poorest for the tests. However, with p-aminophenol sodium hydroxide may give the best results. 2 . Excess alkali is to be avoided as it tends to inhibit the reaction. 3. VkIere reaction takes place with compounds substituted in the coupling position the efficiency of the alkali in promoting the reaction is given by the series: sodium bicarbonate > sodium carbonate 2 ammonium hydroxide > sodium h j droxide. With aminoantipyrine it makes little difference which of the first three alkalies is used. CONCLUSION
I t has been shown that aminoantipyrine 1. Keeps well. 2 . Produces clean-cut reactions with negative controls. 13. Is not too sensitive to the type of alkali. 4. Forms solutions of well-defined colors in day or artificial light. 3 . Is :L sensitive reagent for most phenolic compounds. From these facts it may be concluded that it is a better reagent for phenolic coinpourids than the other amines tested which are deficient in one or more of the items listed above. It appears that it may also be more useful in those cases where the color reactions might give clues to the structures of the phenolic compocnds.
228
EMERSON, KELLY, BEACHAM, AND BEEGLE
229
CONDENSATION OF AMINOANTIPYRINE
I
I -G %
cec:
Mp:
&
m a
mrn
MO
3O
cup:
mffi
*
-I*
c:
lop:
NO
230
4
EMERSON, KELLY, BEACHAM, AND BEEGLE
CONDENSATION OF AMINOANTIPYRINE
* I * I NO
NU m: ea::
m &
3
nF9 us3
nb-
n W
3
*p:
3
I /
*F4
mp:
* I
*F9
bus&
m &
EMERSON, KELLY, BEACHAM, AND BEEGLE
z 0
d
u
.e
0
B
P
a
b
e
ce
‘0
5
+?
c
e
-$ $
2
h
; 8“! m
CONDENSATION OF AMINOANTIPYRINE
I
I I
* I
mp:
NP:
do
Mp:
3;*
mP:
InP:
30
MP:
*
3.2
InP:
mP:
mP:
Mp:
hlb
* I
InP:
In&
In&
MP:
*a
3p:
3P:
3P:
30
I I
M &
MP:
3p:
Mp:
In0
Mp:
mP:
NP;
MP:
loa
MP:
MP:
m&
MP:
m a
* +-
0
3h
0
dp: 0
m&
pi
0
I Gl
+-
p:
p:
P:
233
234
EMERSON, K E L L Y , BEACHAM, AND B E E G L E
EXPERIMENTAL
The tests were made on samples of the phenolic compounds by the second technique described in a previous article (4). THE COLOR^ ALKALIZING AGENT
OF THE
SOLUTIONS OF
. . , . . . . .. . . . . . .
COUPLING AMINE
.I
KaHCOa aq. layer 16
Y p-Aminodimethylaniline
p- Aminophenol
SaiCOa
NaOH
__
Aminoantipyrine
p-Phenylenediamine
TABLE I11 CONTROLS WHEN POTASSIUM FERRICYANIDE IS THE OXIDAKT
THE
3 R
i:
CHCla layer
aq. layer
1 Y
CHCla layer
aq. layer
CHCla layer
aq. layer
1
1
Y
Y
R
2 RO
2 RO
Y
Rb
1 Yb
2 Yb
Y
CHCls layer
-
1 0
1
OY
1 1 bY YG __ __ The method of recording the ca rs of the controls is the same as that used in Table I. See footnote a of that table. b A 1-Y test in the control is due t o the yellow color imparted to the solution by potassium ferricyanide.
-
1
Y
SUMMARY
Aminoantipyrine 3s a reagent for phenols as compared with p-aminodimethylaniline, p-phenylenediamine, and p-aminophenol and was found to be superior t o them. For the promotion of the color test sodium hydroxide was found to be the poorest alkalizing agent and sodium bicarbonate probably the best. HARTFORD, CONN. REFERENCES (1) (2) (3) (4)
Part IV, J . Org. Chem., 8, 433 (1943). EMERSON et al., J . Org. Chem., 8, 417437 (1943). EMERSON AND BEEGLE, J . o r g . Chem., 8, 436 (1943). EMERSON, BEACHAM, AND BEEGLE, J . Org. Chem., 8, 427 (1943).
