ABSTRGT OF THE THESIS OF
Darrell Sinclair harria for the Iiaster of Science in Chemistry
Date Thesis presented
Title
IJay 17,
l9L
2-Nitro-1,3-inandione and it
use as a
reaent for the identifi-
cation of orranic bases
bstraot Jpproved
new reagent, 2-nitro-1,3-indandione, was prepared by G. Wanag in
1936 and. applied to the identification of organic bases. Though later
1iul1er, and L. Rosenthaler appear in the literature,
results by anag,
no studies of this reagent have been reported by workers in this country.
2-Nitro-1,3-indandione behaves as a strong acid and readily forms
salts with orgaric bases. These salts were found to be crystalline, nonhygroscopic compounds which with but few exceptions gave sharp melting
points. Further, many of the salts viere found to dissociate completely
enough in aqueous solution that the neutralization equivalent of the salt
could be determined by titration with standard alkali.
Since relatively few derivatives of heterocycles have been reported,
the work reported here is concerned principally with this class of compounds. Over one hundred derivatives were prepared including salts of the
aliphatic and aromatic amines and heterocyclic bases.
Tables are included listing all the derivatives appearing in the literature as well as analytical data for those salts prepared for the first
time.
2-NITho-1,3-INr.)ANDION:E AND ITS USE AS
1LàGENT FOR TUL IDENTIFICATION
OF ORGANIC BASES
by
DARRElL SINCLàIR HARRIS
A THESIS
submitted to
OREGON STATE COLLEGE
in partial fulfillment of
the requirements for the
degree of
iASTER OF SCIENCE
June l9/
APPROVLD:
Professor of Chemistry
In
Charge of
iajor
Chairman of School Graduate Committee
Dean of
Graduate School
ACKNO1LDENT
Grateful acknowledgment is made to the Shell
eUowsb!p
Corn-
mittee, Mr, E.A. Cunningham, Secretary, for a Shell Graduate Re-
search Fellowship without which this work would have been impossible.
The author wishes also to express his appreciation to Dr. B.E.
Christensen for his many helpful suggestions.
TABI
INTRODUCTION
,
i
. . . . . . . . . . . . . . . . . . . . . . .
3
. . .
EER.II1ENTAL .
OP CONTENTS
. . . . . . .
TABLES:
. . . . . .
,.,.....
..,..... ....
SALTSOFTHALIPliATIC411INES , . .
SALTSOFTkRATIGAIiI1S
. 4
7
. . . . . . . . . .
U
. . . . . . . . . . . . . . . . . . . . . . . .
13
. . . . . . . . . . . . . . . . . . . . . .
14
SALTS OF TH
SULA.RY. . . .
. . .
BIBLIOGR1PHY , . .
UThROCYCLIC COkiPOUNDS .
2-NlTR-1,3-IDIOIE AD
FOR
T1ff
Ii
In 1936
anag
ITS USE
£
REAGENT
IDENTIFIGATIO1'i OF ORGâIIU ]3ASES
TRODUCTION
described a new reagent 2-nitro-1,3-indandione
which Lormed salts with both inorganic cations and organic bases such
a
the aliphatic, aromatic amines and the nitrogen heterocycles.
reported these derivatives to be crystalline, non-hygroscopic,
I-le
vater
soluble compounds which for but few exceptions gave sharp melting
points.
Rosenthaler
applied the reagent to the study of alkaloids
but other than reporting crystal formation gave no analytical or melting point data
Later
iuner
extended the work to a number of mis-
cellaneous compounds such as histamine, tyramine and arginine.
'lork-
ers in this country have been slow to appreciate the possibilities of
this reagent.
2-Nitro-1,3-indandione is
a
strong acid hence most of its amine
salts hydrolyze in acueous medium to yield an acidic solution.
The
extent of the hydrolysis depends on the ionization constant of the
base used in the preparation which in many instances is so small as to
permit the titration of the free acid thus making it possible in these
instances to determine the neutralization equivalent of the salt.
This property is not possessed by usual amine derivatives,
(phenylthio-
ureas, sulfonamides) and coupled with its non-hygroscopic character,
sharp melting point range and ease of preparation makes the 2-nitro-1,-
3-indandione appear as an unusually promising reagent for the identi-
fication of organic bases.
?or these reasons the work of Variag was
continued in this laboratory with particular attention to the acid
properties of the derivatives.
Davies in his studies of this reaction found that acetone was a
supeiior solvent for the preparation of the salt since both the organic
bases and free acid
ere usually soluble in this medium while the salts
either precipitated immediately or slowly crystallized.
1or this rea-
son most of the derivatives used in this investigation were prepared in
an acetone medium.
Except for those compounds in which the nitrogen was not function-
ally basic such as uracil,
nthine, and acetanilide,
derivatives with this reaent.
all others gave
The alkyl amines gave crystalline
salts
which did not hydrolyze sufficiently to give neutralization equivalent
measurements.
The bulk of the nitrogenous bases however gave deriva-
tives which could be titrated with few exceptions (due to color interference)
In certain cases such as the titration of the 4-quinazolone derivative abnormal amounts of alkali were used.
This was due to the par-
tial neutralization of the enol form of the quina zolone.
In every in-
stance in which the ionization constants of the bases were known to be
less than
i06
the indandionate derivative gave correct titration val-
ues (with the certain exceptions cited above).
In border line cases it
was often possible to obtain the correct neutralization equivalent by
merely titrating the solution hot.
Considering the usefulness of this type of derivative in heterocyclic work and the fact that only a limited number of such derivatives
were described by 1danag and others most of the preparative work was de-
voted to hetorocyclic compounds.
EERIIiNTJiL
2-Nitro-]..,3-indandione was prepared according to the directions
¿tpproximately 0.15 g. of the test compound was dis-
of
solved in a minimum amount of acetone, alcohol or water and then added to an excess of the saturated solution of the reagent in the corres-
ponding solvent.
Salts which did
riot
crystallize immediately were
placed in the refrigerator for several hours, then filtered, washed
and recrystallized from ethanol, water or aqueous alcohol.
The neutralization equivalents were determined according to the
directions of Niederl and
Niederl(2668)
using phenolphthalein
indicator.
All the published data together with that obtained in this laboratory are
4ven
in the following tables.
Analytical data are given only
for those compounds which have not been previously described in the
literature.
IT 0F
T}
LIPHATI0
Theory
IkikLE
.nimonia
1ethy1amine
Ethylamine
n-Fropylamine
n-Butylamine
iso-Butylamine
n-Amylamine
io-àmy1aiidne
io-hexy1am1ne
n-Heptylandne
n-heptadecylamine
11y1amine
Iie thylenedi.amine
Ethylenediamine
Propylenediamine
Futreseine
permine
DiinethylantLne
Die thylamine
Dipropylaniine
Dii sobutylamine
Dilsoamylamine
Di-n-hexylamine
Di-2ethy1hey1arnine
%II
;C
iINßz
N.E.
Found
%H
%N
C
Found
o1vent Reference
%H
222
2035
203
N.T.
N.T.
N.T.
*
*
*
N,T
**
N,T.
**
184-5
147
178
158
162
155
149-50
118-9
180-1
229
204-5
206
---
(4)
(6)
(6)
(6)
(5)
(6)
(5
(5
(5
(6
(6)
(6)
(5)
(6)
(
5)
(
5)
(5)
210
N.T,
*
180-1
N.T.
*
210
23].
190
N,T.
114-15
148
* - water
66.99
69.42
- alcohol
- acetone
N,T. - not titratablo
8.57
67.15
9.32
69.07
8.80
9.30
NET.
N,T.
(6)
(6)
(6)
(6)
(6)
Theor
iiFI
Ii
.P.
Di-n-octylamine
96
Trime thylamine
162
Trie thylamine
oil
111
Triisobutylamine
Benzylamine
180
a -P he nylethylamine
207
b-Phenylethylamine
169
b-Phenylisopropylamine 193
Benzhydrylamine
205
L)ibenzylamine
Cyclohexylamine
Camphylamine
Bornylamine
£iicyc1oher1amine
203
213
169
211
222
c
6.47
69.42
N.B,
J?ound
%H
9.32
iound
Solvent
Reference
%N
7.05
68.49
N.T,
9.29
(6
(6
(6
(6
(6
(6
N T.
(5
(6
381
343
67.72
7.58
67.98
N .T,
(6
(6
347
(6
(6
*
7.75
ALCOHOL
Diaminopropanol
6-Aminohexno1-1
195
oil
(5)
ACID
Glycine
a-Aianine( dl)
Creatine
Arginine
--
197-98
---
51.43
48.45
4.32
4.38
51.40
48.37
4,38
4.72
266
280
322
253
266
318
*
(1)
*
(1)
'-n
Found
Theory
,uIDE
Urea (i H20)
cetanide
Guanidine
Idethyl Guaiiidine
Acetamidine
Sernicarbazide
M .P
160
oil
258th
-240
187-90
C
15,&) 44.61
%H
4.12
G
15.85
44.57
NE.
Found
29
271
Solvent
4.26
*
*
NT.
45,12
3.79
44.95
Reference
%H
4.01
266
N,T.
264
*
*
(6
(1
(6
SALTS 0F THE .tROETIC
Theory
AJvIINES:
N.L.
Found
284
284
298
290
312
312
316
305
298
298
296
296
298
294
192
326
329
Xylid.ine-1,3,5
192
185
196
218
312
312
311
312
o-Arninodiphenyl
m-Áxninodiphenyl
183
198
p-Aminodiphenyl
a -Naphthylamino
199
209 -10
193
360
368
335
333
IIaPLE
1i.P,
Aniline
o-Ethy1aniline
209
%C
Found
H
%N
C
$o1vent Reference
%H
(z.)
183
p-Ethylanilino
181
thyle iiodianiline -Nethy1ani1iiìe
186
N,N-Dime thylaniline 133
N-Ethylaiüline
183
Me
N-Propyla niline
N-Butylanilìne
N -isobu.tylaniline
190-1
Pseudocuniidino
162
197-8
193-4
192-3
150
149
190
kieidine
o-Toluidine
m-Toluidine
p-Toluidine
o -Dime thyltoluidine
p-Die thyltoluidine
N-Iiethy1, o-toluidine
N-Ethyl, o-toluidine
209
207
162
N-Ethyl,p-toluidine 164
Xylidine-1,3,4
Xylidine-J.,
3,2
Xylidine-1, 4, 2
B-Naphthylamine
334
334
*
Theory
3ThIPLE
%G
N.E.
Found
%H
%0
Found
,N-Dimethyl,a-naph- 153
thylainine
N-ethy1,B-naphthy1- 177
(6)
N
(5)
amine
Tetrahydro,a-naphthylamine
Te trahydro,B-naph-
thylamine
o-Phenylenediamine
m-Pheiylenedlamine
p-Phonylenediam.ine
Toluylenediarnine-
Solvent Reference
%li
204
(6)
233
(6)
(6)
172-4
200
261-3
60.21
4,38
59.88
4.54
299(1A) 301
245(2A) 246
(6
(6
183
(6)
Naphthyl enediamLne- 179
(5)
Naphthylenediamine- 216
(5)
2-Aminofluorene
(6)
1,2,4
1,2
1,8
195
2, 7-Diaminofluorene 240
Benzidine
213d.
o-Tolidine
216
p,p' -Dianilnodiphen-
248
ylrcie thane
Diphenyline
isobutylbenzylarnine
220
-
(6)
(6)
297
298
(6
(6
(5)
(
5)
ct
NE.
Found
203-5
300
296
210
300
300
306
Found
Theory
}hEI0L
Lì
o-Lminophenol
m4ìminophenol
p-.minopheno1
2,4-Dia mi nophenol
1 -.minonaphtho1-2
Tyramine
C
H
o1vent Reference
C
--
298
(5)
(5)
(5)
(5)
(5)
-
198-200
---
(i)
ETHER
o-Phenetidine
m-Phenetidine
p-Phenetidine
206
o-nìcidine
198
205
203
226
m-.nisidine
p-tnisidine
o-Dianisidine
210
190
328
314
331
312
(5)
(5)
(5)
(5)
314
313
313
308
(5)
(5)
318
318
318
315
317
314
(5)
(5)
RI0GEN
o-Ohloroaniline
m-Chloroaniline
p-Ohloroaniline
182
192
188
o-Nitroaniline
m-Nitroaniline
p-1itroani1ine
144-5.5
3-Nitro,4-aminotolueno
54.67
54.58
3.36 329
328
N.T,(color)
182
175
147-50
3.37
329
56.00
3.82
55.97
4.34
321
1I.T.(color)
(5)
(5)
ÌE**
**
(5)
(5)
Found
Theory
CRB0NYL
4-Arninoa cetophenone
2-Axainoa cetophenone
p-Die thylarninobenzaldehyde
i
.P.
0
li
C
199
163-65
114-15
62.58
65.20
4.32
5.47
62.14
65.02
Solvent
Reference
N .L
found
326
326
368
320
332
375
164
104
163
164
342
337
367
341
364
(
340
N.T.
(6)
(6)
H
4.20
5.72
(5)
ACID AD ACID
DER VATI VE
o-Aininobenzoic acid
rn-Aminobenzoic acid
p-Arninobenzoic acid
1-Tyroine
Methylanthranilate
Ethylanthranilate
Sulfa nilaraide
189
212
213
oil
p-Aininoacetanhlide
Benzarnidine
150-51
197
214
212
195
Novocaine
oil
(5)
59.66
4.14
59.76
4.24
(
5)
(5)
(5)
*
5)
AZO AND AZINE
hydra zine
henylhydra zine
p-âminoa zobenzene
Dia zoaminobenzene
2,4-Dia mi nba zobenzene
Azirninobenzene
---
48,43
4.07
4E.67
4.10
223
299
62.17
3.65
62.08
4.31
290
-
176-78
227
301
N.T.(color)
287
*
«*
--
(
178
(5)
5)
SALTS OF
IROCYCLI0 0OF0UNDS:
i1peridine
Pyridine
a-Picoline
B-Ficoline
g-Ficoline
--
a -turiìnopyridlne
197
235
146
155
187
2 , 6-Biarnìnopyridine
Collidine
Quinoline
Isoquinoline
4.-hie thyiquinoline
6-Methyiquinoline
thyiquinoline
8vie thyiquinoline
7e
5-iiethy1,8-nitro-
quinoline
5-Nitroquinoline
8-Nitroquinoline
5-Bromo, 6-nitroquinoline
4, 7-Dichioroquinoline
cridine
2-Methcȍy,6,9-dichloroa cridine
2, 4-Dime thy1quinizoline
%C
N.E.
Found
Theory
%i\l
%H
N
%G
168
270
163.
284
284
284
286
63.38
63.38
142
113-114
197-8
156-58
167
63.22
62.89
4.25
4.25
Found
4.28
4.23
N,T,
272
278
281
278
284
Reference
(6)
(6)
(6)
**
(6)
(
68.25
4.22
325
312
68.11
4.22
334
334
332
330
3.56
379
371
365
365
369
356
444
453
8.74
8.38
320
320
5)
(6)
(6)
(5)
(5)
(6)
160
i
Solvent
%H
s
157-58
153-54
139
60.16
3.45
59.92
59.20
59.20
48.67
3,04
3.04
2.27
58.87
58,88
48,86
3.23.
2.59
55.12
2.54
389
386
58.85
3.01
58.89
3.20
370
469
373
460
60.54
3.29
60.33
3.43
337
317
156-58
183
139
3.16
2.38
(6)
oil
4-Hydrorquin zoline 196
12.45
12.43
I-j
I-j
Found
Theory
N.E.
FouxI
372
314
Solvent
Reference
L- .
7-Chioro , 4-hydroxyquina zoline
Pipera zine
Pyrrolidine
Guanine
Morpholine
Benzimidazole
3, 5-Diniethy1pyrazole
Nitron
hi$tamine
histidine
5 -àminoura cil(
193
11.31
54.94
2.71
11.27
54.93
2.73
215
-216-17
228
--
49.12
2.95
56.09
5,07
48.75
55.91
3.03
5.56
20)
Creatinine
Pipecolinic acid
-
337
N.T,
*
(
5)
(
5)
(1)
29
16.66
---
134-35
342
(5
(5
(5)
----
1-liydroxyproline
*
N.T.
8,28
47.08
52.16
51.30
53.27
3.60
4.38
3.98
5.37
57.35
57.52
59.66
3.21
3.54
4.12
16.48
8.36
263
315
311
318
*
*
*
*
*
46.76
51.77
50.90
53.34
3.84
4.77
4.06
5.50
336
322
57.17
56.94
59.42
3.66
157
313
342
161
314
339
525
521
*3-*
347
385
371
329
379
351
*
322
338
334
(1)
(1)
(1H20)
Nicotinic acid
Nicotinarnide
Ethylnicotinate
168
191
128
3.93.
4.10
AIKbLQID
uiine
Strychnine
Brucine
Cinchonine( 1H20)
Caffeine
Theobrorriine
186
226
185
166-67
177
(6)
(3)(6)
(6)
8.06
64.00
53.00
51.76
4.91
3.92
3.53
7,98
64.16
53.20
52.10
5.12
3.93
3.87
*
(3)
1-J
13
The use of the indandionate derivatives as a means of obtaining
the neutralization equivalent of the weaker organic bases is demon-
strated.
Over one hundred different derivatives were prepared and
studied, including over forty which have not appeared previously in
the literature.
The data indicates that the salts of bases with a
dissociation constant of less than 1 x 1O
can be titrated.
The potential usefulness of this reagent is extremely promising
considering the sharp melting points of it
derivatives, ease of pre-
paration and possible neutralization equivalent values.
14
ElE
1.
L.uller, Ernst.
O GRAPH!
Uber das 2.-nitro-indandion-(l,3) als basenZ. Physiol. Chem.
269:31-2 (1941).
fllungsmittel.
2.
Niederl, Joseph B. and Niederl, Victor.
niicroanalysis. 2d ed. New York,
Inc.,
1942. 347p.
3.
Rosenthaler, L. 2-Nitroindandion-1,3
Scientia kharm. 9:4 (l93).
4.
Wanaz, Gustave.
69B:1066-74
Organic quantitative
John Wiley and sons,
als
reagens
aul'
basen.
2-nitro-indandion-(l,3) und seine salze.
(1936).
Ber.
5.
Wanag, Gustave and Dombrowski, Anna.
6.
Wanag, Gustave and Lode, Arnold. Verwendung von 2-nitroindandion-(l,3) fur die Isolierung und identifizierung organischer basen. Ber. 70B:547-59 (1937).
Verwendung von 2-nitroindandion-(l,3) für cue isolierung und identifizierung
organischer basen, II. mitteilung. Ber. 75B:82-6 (1942).