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The Valence of Nitrogen in Am-
monium Salts -
BY
RALPH. S. POTTER
A.B. Lake Forest College, 1909
M.S. University of Illinois, I9 II
A THESIS
SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR
THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY
IN THE GRADUATE SCHOOL OF THE UNI-
VERSITY OF ILLINOIS "
- I913
EASTON, PA.:
SCHENBACH PRINTING COMPANY
-* I9 I4. -
The Valence of Nitrogen in Am-
- monium Salts
BY
RALPH. S. POTTER
A.B. Lake Forest College, 1909
M.S. University of Illinois, I 91 I
A THESIS
SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR
THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY
IN THE GRADUATE SCHOOL OF THE UNI-
VERSITY OF ILLINOIS
I9 I3
EASTON, PA.:
EscHENBACH PRINTING COMPANY
I9I4.
The Valence of Nitrogen in Ammonium
Salts
During the early years of the development of the theory of valence,
many chemists held the view that each element has an unvarying valence.
The apparent change of valence in nitrogen from ammonia to ammonium
salts, and in phosphorus from phosphorus trichloride to phosphorus penta-
chloride was explained by calling the ammonium salts and the pentachloride
molecular compounds, as distinguished from ammonia and the trichloride,
in which the true valence of the elements was supposed to be shown.
This view received support from the dissociation of ammonium salts
and of phosphorus pentachloride in the gaseous state. Gradually, with
the demonstration that phosphorus pentachloride volatilizes in part un-
changed, that phosphorus pentafluoride, PFs, has a vapor density corre-
sponding to its formula and, in general, that dissociation in the gaseous
4.
state does not correspond to any rational distinction between unitary and
molecular compounds, the view that elements may show a varying valence
in their compounds and that nitrogen and phosphorus are sometimes triva-
lent and sometimes quinquivalent, came to be generally accepted.
More recently, Werner' has proposed a modified molecular formula
for ammonium chloride, H3N. . . HC1. By this formula he intends to indi-
cate that in the ammonium salts the nitrogen atom retains a normal valence
of three, but that the nitrogen atom of the ammonia and the hydrogen atom
of the hydrochloric acid are held together by secondary (“Neben”)
valences, the hydrogen and chlorine of the acid retaining essentially the
same relation to each other as in the free acid.
An amino acid may, theoretically, assume in the aqueous Solution the
CO2H - / CO
following forms: a, the free acid, RS ; b, a cyclic salt, RQ Xo,
NH2 - NH3
CO. — O
or according to Werner, RQ : ; c, a bimolecular or polymolecular
- NH2—H
CO2—H3N
salt formed by the union of two or more molecules, RQ XR.
* - NH3—O2C
CO2T
d, the ions of the acid group RS and Hºt; e, the ions of the base,
NH2
2CO.H CO2-
and OHT; f, the double, amphoteric ion, R .2
- NH3+
The “inner salt” structure was first proposed by Erlenmeyer and
Siegel” in 1875. Ten years later Ostwald" noticed that solutions of glyco-
coll, CH3NH2CO3H, have a very low molecular conductivity and that this
is only slightly increased by dilution. He states that in its behavior it
is more like a neutral salt than an acid. In 1891 Marckwald" called at-
tention to the fact that amino acids of the aliphatic series react only slowly
with the mustard oils, while other primary amines react quite readily.
Since the amino acids react easily in alkaline solutions, he held that the
acids are, in reality, inner salts. Sakurai" attempted to substantiate the
“inner salt” structure on their preparation from halogen derivatives of
the acids and on the resistance which amino acids offer to the formation
of acid chlorides. Walker" points out that conductivity determinations
R
NH,
* See Neuere Anschauungen auf dem Gebiet der anorganischen Chemie, 1905, p. 96.
* “Zwitterion.”
* Ann., I'76, 349 (1875).
* J. prakt. Chem., 32, 369 (1885).
* Ber., 24, 3278 (1891).
* Proc. Chem. Soc., Io, 90 (1894).
* Ibid., Io, No. 139 (1895).
5
tell us very little about the structure of glycocoll, but that, since the con-
ductivity of phenylglycocoll, CGH;NHCH3CO2H, is greater than that
of acetic acid, it must contain a carboxyl group which ionizes. Tilden and
Forster' showed that the amino group of amino acids may be replaced
by chlorine by the action of nitrosyl chloride, and considered this an argu-
ment against the inner Salt formation. Somewhat later Carrara and
Rossi” based an argument for the inner salt structure on the conductivity
of betaine hydrochloride, (CH3)3MC1CH3CO2H. From the values found
they considered that the salt was almost completely hydrolyzed to hydro-
chloric acid and betaine, (CH3)3NCH2CO. Winkelblech” points out,
No/
however, that if betaine hydrochloride is in reality hydrolyzed the con-
ductivity of the solution should be the same as that of the equivalent amount
of hydrochloric acid, while both Bredt's measurements and those of Car-
rara and Rossi gave a conductivity scarcely more than one-half as great.
There can be no doubt, of course, that the anhydride of betaine,
(CH3)3MCH2CO2, has the structure of a salt, but no one seems to have
determined whether this is monomolecular or dimolecular. Walker*
CO2H
has shown, however, that aminoacetic acid, Cºssa , is monomolecular
2
in aqueous Solutions. Our results, given below, indicate that a solution
of an amino acid which gives no inner salt may still contain the acid mostly
in the monomolecular form.
Winkelblech" discusses the hydrolysis of an amino acid on the basis
of conductivity data for weak acids, weak bases and water. It does not
seem possible from conductivity data, however, to determine whether the
CO2
acid is in the form of an inner salt, RK
| in the unionized state,
NH3
, in the form of the double, amphoteric ion
R or R
\NH, NN H3OH
/co- /co-N Hs
RS , or in the form of a bimolecular salt, RS 2R. The
NH3+ NH3—CO2
hydrogen and hydroxyl ions of the amphoteric form would, of course,
combine to form water and if the acid and basic functions were of equal
“strength” the solution would react neutral. None of these forms would
show any conductivity and, while the bimolecular form could be distin-
* Chem. News, 71, 239 (1895).
* Atti R. Accad. Lincei, [5] 6, 208 (1897).
* Z. physik. Chem., 36, 590 (1901).
* Proc. Chem. Soc., Io, 94 (1894).
* Loc. cit.
6
guished from the others by a determination of the molecular weight, it is
not clear how any of the ordinary physical methods could be used to dis-
yco H CO2 /co-
tinguish between the three forms, RS y R& | , and RS e
+
CO2H NH2 NH3 NH3
The form RQ would have a higher molecular weight and might,
NH3OH
possibly, be distinguished from the other three by that means, but it could
not be distinguished by conductivity measurements. It does not seem
to us that the ordinary equations for hydrolysis, which Winkelblech at-
tempts to apply, could be used in a complex case of this sort.
From the above summary it would seem that the evidence with regard
to inner salt formation is not altogether satisfactory and light upon the
question from an entirely different point of view is welcome. We think
that we have secured this from a study of the specific rotations of a series
of amino acids from camphor. The formulas and names of the compounds
are given below. To bring out the relationships more clearly the specific
rotations given for the salt are calculated to the basis of one gram of the
free acid in I ce. of the solution instead of for one gram of the salt.
CH2—C(CH3)—CO
scº. O
CH2—CH NHs
Aminocamphonanic Acid.
[o]o = —29.2 °.
CH2—C(CH3)—CO2H
C(CH3)2
CH2—CH-NH3Cl
Hydrochloride of Aminocamphonanic
Acid. [o]p = 25.0°.
CH2—C(CH3)NHs
C(CH3)2 O
CH2—CHCO
Aminodihydrocampholytic Acid.
[o]n = 53.7°.
CH2—C(CH3)NH3Cl
C(CH3)2
CH2—CHCO2H
Hydrochloride of Aminodihydro-
campholytic Acid. [o]p = 41.3°.
CH2—C(CH3)—CO
scº
CH2—CH NH
Anhydride of Aminocamphonanic
Acid. [o]p = —60.5°.
CH2—C (CH3)—C O2Na
C(CH3)2
CH2—CHNH2
Sodium Salt of Aminocamphonanic
Acid. ſold = 52.8 o,
CH2—C(CH3)—NH
scº
CH2—CH CO
Anhydride of Aminodihydrocampholytic
Acid. [o]p = 72.8°.
CH2—C(CH3)NH2
C(CH3)2
CH2—CHCO2Na
Sodium Salt of Aminodihydro-
campholytic Acid. [o]p = 18.3°.
CH2—C(CH3)—CO2H
toº.
CH2—CH-CH2NH2
o:-Aminocampholic Acid.
[o]o = 67°.
CH2—C(CH3)—CO2H
º CH3)2
CH2—CH-CH2—NH3C1
Hydrochloride of o-Aminocampholic
Acid. [o]p = 44.7°.
CH2—C(CH3)—CH2NH2
C(CH3)2
CH2—CH-CO2H
8-Aminocampholic Acid.
[o]d = 16.4°.
CH2—C(CH3)—CH2NH3Cl
| C(CH3)2
CH2—CH-CO2H
Hydrochloride of 3-Aminocampholic
Acid. [o]p = 41.3°.
C(CH3)2 NH
|
CH2—CH CH,
Anhydride of o-Aminocampholic
Acid (o-Camphidone). [o]p = —33.9°.
CH2—C (CH3)—CO2Na
scº
CH3—CN–CH2—NH2
Sodium Salt of o-Aminocampholic
Acid. [of]o = 62.4°.
CH2—C(CH3)—CH2
C(CH3)2 NH
| |
CH2—CH CO
Anhydride of 3-Aminocampholic Acid
(3-Camphidone). [o]D = 66.5°.
CH2—C(CH3)CH2NH2
C(CH3)2
CH2—CH-CO2N al
Sodium Salt of 3-Aminocampholic
Acid. [o]p = 14.3 °.
It will be noticed that the aminocamphonanic acid and aminodihydro-
campholytic acid are represented as having a cyclic or inner salt structure,
while the aminocampholic acids are both represented as having an open
structure. The evidence for these structures is based on the specific
rotation of the compounds. The rotation of the sodium salt and hydro-
chloride of aminocamphonanic acid are to the right while that of the an-
hydride, which is undoubtedly cyclic in structure, is to the left. The
ammonium salt is also left handed, indicating a cyclic structure similar
to that of the anhydride. The Sodium salt and hydrochloride of amino-
dihydrocampholytic acid are right handed. The free acid and anhydride
are also right handed, but with a considerably increased rotation. The
sodium salt and free o'-aminocampholic acid are both right handed with
rotations closely alike, indicating that each has an open structure, but the
anhydride, which certainly has a cyclic structure, is left handed and has
a rotation very closely like that of the aminocamphonanic acid, indicating
again very clearly that the latter has a cyclic structure and that each
compound contains a cycle of Six atoms. The sodium salt of 3-aminocam-
pholic acid and the free acid also correspond closely in rotation, indicating
8
an open structure for both, while the hydrochloride and anhydride have
a considerably greater rotation, as is the case with both the free amino-
dihydrocampholytic acid and its anhydride.
All of these observations are consistent with the hypothesis that amino-
dihydrocampholytic and aminocamphonanic acid form cyclic Salts con-
taining cycles of six atoms, while the aminocampholic acids do not form
such salts, because, if formed, they would contain cycles of Seven atoms.
It seems dfficult to find any other simple explaflation for the observations.
The results also point very strongly to the formula for ammonium salts
which represents them as containing quinquivalent nitrogen and against
Werner's formula. According to Werner's formula the free aminocam-
phonanic and aminodihydrocampholytic acids would contain cycles of
Seven atoms,
CH2—C(CH3)—CO—O
C(CH3)2 H
CH2—CH-NH2
Such a formula is quite inconsistent with all that we know about the ease
with which rings of five and six atoms are formed and the comparative
rarity of seven-atom rings. It is also inconsistent with the close agree-
ment between the rotation of the aminocamphonanic acid and that of the
anhydride of o-aminocampholic acid. We know that the latter compound
contains a six-atom ring.
Determinations of the molecular weights in aqueous solutions by the
freezing point method have shown that all four of the amino acids are
monomolecular in such solutions.
The following table brings out in a striking way the relations which have
been found. The rotations are calculated from results obtained with
solutions containing from 2.5 to 10% of the substances examined and are
given on the basis of the amount of free amino acid corresponding to the
compound which was present. Thus [o]n for the hydrochloride of
aminocamphonanic acid (i.e., the rotation in a 10 cm. tube of I g. in I ce.)
is 25.0° but the rotation in the table is given as 30.3°, which is the calcu-
lated rotation for I g. of the free acid in I co., after conversion into the
hydrochloride.
HC1 HC1
salt —- salt —-
HC1 Free 1 mol 2 mols Anhy-
salt. acid. NaOH. NaOH. dride.
Aminocamphonanic acid. . . . . . . . . . . . 30.3° —29.2° —28.8° 55.4° —60.5°
Aminodihydrocampholytic acid. . . . . . 5o. 1 ° 54.7° 54. O' 20.5° 72.8°
o:-Aminocampholic acid. . . . . . . . . . . . . 53.3° 67.0% 62.4° 65.6° —33.9°
8-Aminocampholic acid. . . . . . . . . . . . . 49.5° 16.4° 16.7° 15.2° 66.5°
The free acids have, in each case, nearly the same rotation when prepared
by the addition of one mol of sodium hydroxide to one mol of the hydro-
S.
9
chloride, as when the pure acid is dissolved directly in water. The addi-
tion of a second mol of sodium hydroxide causes a large change in the ro-
tations of aminocamphonanic and aminodihydrocampholytic acids, evi-
dently because the cyclic structure of the inner salt is broken down by the
formation of the sodium salt, but no such change is observed with the
campholic acids.
^
Experimental.
CO2H
Aminocamphonanic Acid, ché .—The hydrochloride of amino-
NH2
camphonanic acid was prepared as previously described." One hundred
grams of the hydrochloride were dissolved in water and a solution of so-
dium hydroxide added till the reaction was faintly alkalinetophenolphthalein
after boiling a small portion in a test tube. The solution was then evap-
orated to about Ioo co, and the free amino acid obtained was filtered off
and was recrystallized by dissolving in water and evaporating the solu-
tion. The yield of the crude acid was 72 g., about 82% of the theory.
It is possible to recover the remainder of the acid as hydrochloride from
the mother liquors. The free acid is about equally soluble in hot and
cold water. Hoogewerſ and Van Dorp’ report a melting point of 260°.
If heated rather rapidly we find that it sublimes without melting at a
temperature above 300°. It is probable that the melting point reported
by Hoogewerſ and Van Dorp was found by heating slowly, which causes
a partial conversion into the anhydride. The latter melts at 203 °. Be-
cause of the melting point reported by the authors mentioned, and because
of the left-handed rotation, which seemed to us, at first, anomalous for
a derivative of dextrocamphoric acid, the mother liquors from the prepara-
tion of the aminocamphonanic acid were very carefully examined for a
possible isomer, but none was found.
The aqueous solution of aminocamphonanic acid, Io g. in Ioo ce. of the solution,
gave a specific rotation [a]** = −29.2°.
The molecular weight was determined with a sample which had been
recrystallized six times from water, twice more than was necessary to re-
move all of the chlorine. A solution of the acid was mixed with ice, from
distilled water, which had been broken to pieces the size of a pea and the
mixture was placed in a Dewar bulb. After equilibrium was reached and
the temperature had been taken, 20 cc. of the clear solution were drawn
off and evaporated and the residue dried to constant weight on the water
bath. The results were:
Subst., O.304; H2O, 16.6; depression, O.I.94; mol. wt. found, 173. Calc. for
CaFII3CO2NH2, I7 I.
* Am. Chem. J., I6, 507 (1894). Formerly called aminolauronic acid. See J.
Am. Chem. Soc., 34, IO67 (1912).
* Ibid., 16, 506 (1874), footnote.
IO
CO
The Anhydride of Aminocamphonanic Acid, C.H.K , has been
NH
prepared" by distilling a mixture of the hydrochloride and lime. The
following method gives a nearly quantitative yield and avoids the use of
a high temperature: Ten grams of the hydrochloride, 6 g. (1.5 mol) of
fused sodium acetate, and 20 cc. of acetic anhydride were boiled gently in
a long necked flask for about IO min. After cooling, Io96 excess of a
strong solution of sodium hydroxide was added and the mixture heated on
the water-bath till the liquid layer which formed at first on top was changed
to a solid. The liquid layer probably consisted in part of the acetyl de-
rivative of the anhydride, but this was not examined further. After cool-
ing, the anhydride was separated by two extractions with ether. After
two crystallizations from petroleum ether it melted quite sharply at
2O3°.”
[o]** = —60.5, I g. in Io ce. of absolute alcohol and [o]** = —60.6°, o.o.5 g.
in Io ce. of water. Noyes and Taveau' found [o]** = —60.1° for a 10% alcohol
solution.
Subst., o.373, o.750; H2O, 20.9, 20. I; depression, o.208°, o.432 °; mol. wt. found,
NH
157, 159. Calc. for cº | : I53.
CO
Hydrolysis of Aminocamphonanic Acid Anhydride.—The anhydride
was not hydrolyzed by heating with water for three days in a water-bath.
Heating for three days in the water-bath with an excess of sodium hy-
droxide was also without effect, but when 3 g. of the anhydride were heated
for IO hrs. with 20% hydrochloric acid the Solution deposited crystals of
CO2H
the hydrochloride of aminocamphonanic acid, Całłós , on cooling.
NH3C1
This gave [o]f a 24.9°, proving that there is no inversion of the acid
either in the formation of the anhydride or in its hydrolysis.
CO
Acetyl Derivative of Aminocamphonanic Anhydride, CSFL. e
º NC2H3O
—This was prepared by boiling a mixture of 6 g. Of aminocamphonanic
acid hydrochloride, 3.5 g. Of Sodium acetate and I2 cc. of acetic anhydride
for 10 min. After cooling and adding enough sodium hydroxide to nearly
neutralize the acetic acid and excess of acetic anhydride, the mixture was
extracted with petroleum ether and the extract washed with water to re-
move free acid. After drying with sodium sulfate and distilling away the
1 J. Am. Chem. Soc., 34, 62 (1912).
* Am. Chem. J., 16, 507 (1894).
* Ibid., 32, 288 (1904).
II
petroleum ether, a slightly yellow oil was obtained. This was distilled
and the portion boiling at 260–262° was analyzed:
Calc. for C8H14CONC2H3O: N = 7.16; found: 7.05; [o]D = +72.7°, o.544 g. in
5 cc. of alcohol.
The substance gave aminocamphonanic anhydride melting at 201–203 °
by hydrolysis with sodium hydroxides.
sº 2CO
Nitroso Derivative of Aminocamphonanic Anhydride, CsIHS *
Wº NNO
—This was prepared by Bredt, but he did not determine the specific
rotation.
We found [a]%;" = 153°; O.25 g. in IO ce. Of alcohol.
It is interesting to notice that both the acetyl and the nitroso group
change the negative rotation of the anhydride to a positive, the nitroso
group producing a much larger effect than the acetyl group.
CO2H
Cyanocamphonanic Acid, chº , was prepared by treating
CN
CO2H
of-camphoramidic acid, cº , with acetyl chloride, according
CONH2
to the method of Hoogewerſ and Van Dorp.” This gave about the same
yield of crude acid which they obtained, namely, about 50%. It was
thought, since the hydrochloride of the cº-isoimide obtained by treating
the cº-camphoramidic acid with acetyl chloride is very easily hydro-
lyzed by water to the cº-camphoramidic acid, that perhaps by suspending
the isoimide hydrochloride in petroleum ether and passing in dry ammonia
gas, the yield could be increased. The following procedure was used:
12.5 g. Of cº-camphoramidic acid and 50 g. of acetyl chloride were placed
in a flask which was attached to a reflux condenser. The flask was heated
on the water bath. A solution is first formed and in about two minutes
the contents of flask apparently become solid. The flask and material
were then cooled, the material filtered and the solid washed with carbon
disulfide. Up to this point the method of procedure was just the same
as given by the above mentioned investigators. Instead of adding the
isoimide hydrochloride to 20% ammonia, as they did, it was shaken with
petroleum ether and a slow stream of dry ammonia gas was passed through
the mixture until saturation was reached. A dilute solution of ammonia
was added to dissolve the ammonium Salts, and from the aqueous solution
the cyanoacid was precipitated with dilute hydrochloric acid. The
hydrochloric acid solution must be added drop by drop or the cyanoacid
will be precipitated as a gummy mass. The crystalline acid was filtered
* Ber., 35, 1291 (1902).
* Rec. trav. chim., I4, 261 (1895).
I 2
•º
and, after drying, was weighed. IO g., or 84%, of the theory was ob-
tained. For purification two methods were used, one by recrystalliza-
tion from hot water, which was the method used by Hoogewerſ and
Van Dorp, the other, by dissolving the acid in dilute ammonium hydroxide
and precipitating it with dilute hydrochloric acid. By the first method
from 5 g. of the crude acid 2.4 g. of acid, melting sharply at 121°, were
obtained. This is the melting point found by the above mentioned in-
vestigators. By the second method, 3.1 g, of the pure product were ob-
tained from 5 g. of the crude acid. This method is also to be preferred
on account of its greater ease of manipulation.
[o]** = 67.3°, I g. in 10 cc. of alcohol. Hoogewerſ and Van Dorp' found exactly
the same for a 6% alcoholic solution.
CO2H
o-Aminocampholic Acid Hydrochloride, .—The only
CRH
"NCH.N.H.C.
variation from the method of preparation of Hoogewerf and Van Dorpº
or Rupe and Splittgerber” was that a Somewhat larger portion of sodium
was used in the reduction. 5 g. of cyanocamphonanic acid were dis-
solved in 50 cc. of absolute alcohol and I5 g. Of Sodium were added in small
portions, the flask being connected to a reflux condenser. During the
addition of the sodium about 20 cc. more of alcohol were added. After
all the sodium had dissolved water was added and the solution was evap-
orated until the odor of alcohol was no longer given. From this point
on a method of separation and purification of the hydrochloride entirely
different from that of Rupe and Splittgerber” was used. Hydrochloric
acid in slight excess was added to the cold solution and it was then ex-
tracted with ether in order to remove any unchanged cyanoacid. Upon
evaporation of the ether solution it was found that about I g. of cyano-
acid was obtained. This was used in subsequent reductions. The
hydrochloric acid solution was evaporated to dryness and the residue
ground up in a mortar with alcohol. The alcohol was filtered, diluted,
with water and the alcohol was evaporated. The brown turbidity of the
solution was then removed by filtering twice through powdered animal
charcoal. The clear solution was then evaporated on the water bath
until crystals started to form, when it was removed and allowed to cool
and filtered. The very slightly brown crystals were dissolved in the
minimum amount of hot water, filtered again through animal charcoal
and after cooling, the pure white, needle-like crystals were filtered off,
dried, and a melting point taken. It was found to be 248–250°. A
portion was again recrystallized and the same melting point was given.
* Rec. trav. chim., 14, 26 (1895).
* Ibid., 14, 261 (1895).
* Ber., 40, 4313 (1907).
I3
Rupe and Splittgerber" give the melting point as 247–248°. The specific
rotation, which had never been taken before, was determined.
ſojº" = 44.7°; o.5 g. in Io ce. of a solution in water.
Cale. for C8H14(CO2H) CH2NH2HC1: C1 = 16.oo; found: C1, 16.17.
CO2H
o-Aminocampholic Acid, CeBS .—An attempt was made
CH2NH2
to prepare the free acid from its hydrochloride in the same manner that
aminocamphonanic acid is prepared from its hydrochloride, but the free
acid was apparently more soluble than sodium chloride and this method
was abandoned. Instead, the hydrochloride was dissolved in water and
sodium hydroxide added until an outside test with phenolphthalein showed
a very faint alkaline reaction. The solution, after filtering, was evaporated
to dryness and the residue was ground up in a mortar with alcohol, the
alcohol filtered, diluted and partially evaporated. The slightly turbid
solution was filtered through charcoal and then the solution was evaporated
until only a few cubic centimeters of liquid were left, a large mass of crys-
tals having separated during the evaporation. The crystals were filtered
off and recrystallized by evaporation of the water solution, the acid being
practically as soluble in cold as in hot water. This was repeated three
times more and the acid then showed no trace of chlorine. The molecular
weight was determined with this sample. Heated in a capillary tube
no melting point was obtained but considerable decomposition took place
between 300° and 320°, depending upon the rate of heating.
[o]** = 67.0°; o.207 g. in Io ce. of solution.
Subst., O.418, O.585; H2O, I5.6, 18.4; depression, O.251 °, O.297 °; mol. wt. found,
CH2—NH2
I96, 197. Calc. for cº : I 85.
CO2H
CO
o–Camphidone, cº. XN H.—This was prepared from the
2
hydrochloride of cy-aminocampholic acid in precisely the same manner
as the anhydride of aminocamphonanic acid was prepared from the hydro-
chloride of aminocamphonanic acid. After making the acetic anhydride
solution alkaline with sodium hydroxide the same liquid layer was observed
on the surface that was observed in the preparation of the above mentioned
anhydride. This was very likely the acetyl derivative, but no attempt
was made to isolate it. Practically a theoretical yield of the anhydride
was given. It melts at 229–231 °. Recrystallizing once from petroleum
ether gave a pure product melting at 230–231 °.
[a]?” = —33.9°; O.5 g. in Io ce. alcohol solution. Rupe and Splittgerber" give
[o]o = —37.2° in a 10% solution in benzene.
* Ber., 40, 4313 (1907).
I4.
- co-
Calc. for cº 2NH. N = 8.38; found: N = 8.42.
CH2
CO
Nitroso Derivative of o-Camphidone, chº X NO. — The
CH2
of-camphidone was dissolved in hydrochloric acid (I : 4) and a Sodium
nitrite solution slowly added. The yellow crystals formed were filtered,
dried and recrystallized from hot alcohol. The lemon yellow, needle-like
crystals gave a melting point of 125-126°. The product given by a second
recrystallization showed the same melting point.
[a]** = —59.0°; O.25 g. in IO ce. Of alcohol.
From analogy to the well-known nitroso derivatives of aminocamphonanic
and dihydroaminocampholytic acid anhydrides, it was not thought
necessary to analyze the compound for identification.
NH2
CO2H
pared in the same manner as described by Noyes' except that a more
elaborate method was followed in recovering the last traces of the acid.
The procedure followed was identical with that for the preparation of
aminocamphonanic acid from cº-camphoramidic acid, except that 3-
camphoramidic acid was used and, instead of adding sufficient hydro-
chloric acid to give the acid hydrochloride, only enough was added to give
a solution exactly neutral to phenolphthalein. After this point the Solu-
tion was evaporated until the sodium chloride was starting to come down.
The crystals of the amino acid were then filtered off and to the filtrate
an excess of hydrochloric acid was added and the whole evaporated to
dryness, and the residue extracted with alcohol. Since the dihydro-
aminocampholytic acid is quite easily esterified, the alcoholic solution was
diluted with considerable water and just enough sodium hydroxide solution
added to give a solution neutral to phenolphthalein. It was then partially
evaporated and the amino acid filtered off. An excess of hydrochloric
acid was added to this filtrate and the same procedure followed as above.
Since the acid is no more soluble in hot than in cold water and is not soluble
in any other solvent it must be purified by dissolving in water and partial
evaporation. For ordinary purposes one recrystallization is sufficient.
For taking the molecular weight and rotations an acid was used which
had been recrystallized six times, two more times than was necessary to
free it from traces of chlorine.
Aminodihydrocampholytic Acid, chº .—This acid was pre-
[a]?” = 54.7 °; o.5 g. in Io ce. of water solution. Noyes and Phillips” give [o]p =
* Am. Chem. J., I6, 503 (1894).
* Ibid., 24, 290 (1900).
I5
53.7° for the saturated solution (about 7.5%). Subst., O.415, O.613; H2O, 20.5, 21.2;
- /NH.
CO2H
NH3C1
Aminodihydrocampholytic Acid Hydrochloride, CsIHS .—A
CO2H
depression, O.I.99, O.278; mol. wt. found, 187, 191; Calc. for C8H14 I7I.
few grams of the free acid were shaken with a few ce. of water and sufficient
hydrochloric acid was added to give a green color to methyl violet paper.
The solution was then partially evaporated and upon allowing to cool
the hydrochloride separated. It was filtered and recrystallized from hot
water. A melting point of 262-263° was found. Recrystallizing again
gave a product melting at 261-262°, which is the same as that reported
by Noyes."
[o]} = 41.3°; I g. in 10 cc. of water solution.
NH
Aminodihydrocampholytic Acid Anhydride, CaFLQ | –This sub-
CO
stance was prepared either by treating the free acid with acetic anhydride
or by treating the hydrochloride of the acid with sodium acetate and
acetic anhydride and subsequently heating the mixture with an excess
of sodium hydroxide. In the latter method it is probable that the acetyl
derivative is formed, as the similar liquid layer was always formed on
addition of the excess of sodium hydroxide to the acetic anhydride solu-
tion. The latter method of preparation has the advantage of allowing
quite impure hydrochloride to be used. The melting point, 188–189°,
and the specific rotation, [a]} = 72.8°, have already been published.”
Nitroso Derivative of Aminodihydrocampholic Acid Anhydride,
N NO *
C8H14 & .—Since the rotation of this substance had never been
O
reported it was thought desirable to obtain it. It was prepared according
to a method previously reported.”
[o]** = -83.3°; o.25 g. in Io ce. of absolute alcohol solution.
Cyanodihydrocampholytic Acid.—Hoogewerſ and Van Dorp' pre-
pared this acid in just the same manner that they prepared the cyano-
camphonanic acid. Rupe and Splittgerber" proceeded in essentially
the same manner. Starting with 12.5 g. of 6-camphoramidic acid and
proceeding in precisely the same manner as in the preparation of the cyano-
camphonanic acid, 9.5 g. Of crude acid were obtained, which is an 80%
yield. There was not nearly as much tendency to form a gummy pre-
* Am. Chem. J., 16, 504 (1894).
* Noyes and Potter, J. Am. Chem. Soc., 34, IoT 2 (1912).
* Rec. trav. chim., I4, 267 (1895).
* Ber., 40, 4313 (1900).
I6
cipitate as was noted in the case of the cyanocamphonanic acid. The
crude acid was purified by dissolving in 8% ammonia and precipitating
with hydrochloric acid. One such procedure sufficed to bring the melt-
ing point up to Io9–I IO’. A portion was recrystallized again in the same
manner but no change in the melting point was observed. The above
/is the melting point observed by Hoogewerſ and Van Dorp."
[o]** = 25.3°, o.6 g. in Io ce. of alcohol solution. Hoogewerſ and Van Dorp
give the specific rotation [o]p = 18.12° for a 6% alcohol solution.
Since they purified their acid by recrystallization from hot water, in order
to clear up the remote possibility of this causing the difference in the ro-
tation, some of the crude acid was purified by their method, but a rotation
taken after the fourth recrystallization, gave a value [o].D = 25.2° and
after the fifth recrystallization [o].D = 25.3°, so there is little doubt but
that this is the correct value.
CH2NH3Cl
6-Aminocampholic Acid Hydrochloride, ché .—Starting
CO2H
with cyanodihydrocampholytic acid the procedure for the preparation,
separation, and purification of this substance was the same as the prepa-
ration of the o-aminocampholic acid hydrochloride. It was found, how-
ever, that the reduction in the case in hand was not as complete as with the
cyanocamphonanic acid. It was found more advisable to simply separate
the unchanged cyanoacid by extraction of the acid solution with ether
than to use more sodium and alcohol. The 3-aminocampholic acid hydro-
chloride is somewhat less soluble than its isomer and hence it is more easily
purified. After two recrystallizations its melting point was 218–220°.
[o]** = 41.3°; o.5 g. in Io ce. of water solution.
CH3NH2
6-Aminocampholic Acid, C.H.& .—About 5 g. of the pure
- CO2H
hydrochloride were dissolved in the minimum amount of water and suffi-
cient strong Sodium hydroxide solution (3 cc. = I g.) was added to give
a solution neutral to phenolphthalein. The free acid, which was pre-
cipitated, was filtered, dissolved in hot water, partially evaporated and
filtered. This was repeated until a substance free from chlorine was ob-
tained, three recrystallizations in all being required.
[o]** = 16.4°; o.25 g. in Io ce. of solution.
Subst., O.318, O.389; H2O, 22. I, 21.8; depression, O.I.33, o. 167; mol. wt. found, 199,
CH2NH2
197. Calc. for chº : I 85.
CO2H
CH2
6-Camphidone, cº XH-This compound was prepared from
CO

* Rec. trav. chim., 14, 267 (1895).
17
the 6-aminocampholic acid hydrochloride in just the same manner
as the cº-camphidone was prepared from the cº-aminocampholic acid.
A melting point of 234-235° was found and a specific rotation [oft" =
63.2 °; O.25 g. in 5 cc. of alcohol solution. Rupe and Splittgerber' report
a melting point of 225° and its specific rotation [o]n = 66.5° for a 10%
solution in benzene. An analysis of the compound was made.
4. yco
Calc. for CH& NH = 8.38; found: N = 8.37.
CH2
* CO N
Nitroso Derivative of 6-Camphidone, chº N NO.-The 6-
- chº
camphidone was dissolved in dilute hydrochloric acid (I : 4) and a sodium
nitrite solution was added. The yellow precipitate was filtered and re-
crystallized from alcohol two times, when a melting point of 164–165°
is given. A portion recrystallized a third time showed the same melting
point.
[o]** = 103°; o.25 g. in 10 cc. of solution.
Summary.
It is shown in this paper that the specific rotations of some amino de-
rivatives of camphoric acid are consistent with the view that those amino
acids which can form cyclic salts containing quinquivalent nitrogen and
CO
a ring of six atoms form Salts having the general formula RK Xo
NH3
in aqueous solutions. Amino acids which would give a ring of seven atoms
in forming a cyclic Salt appear to exist in solution as compounds of the
CO2H
form, R& . These relations furnish strong evidence that nitrogen
is in reality quinquivalent in ammonium salts and that the hydrogen
of the acid combines with the nitrogen instead of remaining combined
with the acid radical, as Werner has supposed.
Several new compounds have been prepared and the specific rotations
of a number of known compounds have been determined.
URBANA, ILLINOIS.
ACKNOWLEDGMENT.
This investigation was carried on during the academic year 1912–1913
and was undertaken at the suggestion of Professor W. A. Noyes. This
opportunity is gladly taken by the writer to express his sincere apprecia-
tion for the suggestions which Professor Noyes was always ready to give,
and still more for the inspiration obtained by the personal association
with him in the laboratory.
EIOGRAPHICAL.
The writer graduated from Lake Forest College in 1909 with the degree of
Bachelor of Arts. During the next academic year, 1909–1910, he was As-
sistant in Chemistry at the University of Illinois. For the years 1910–1913
he was Research Assistant to Professor W. A. Noyes. While holding
the latter position, investigations on molecular rearrangements in the
camphor series were pursued. The results obtained, other than those
described in the present paper, were published in the Journal of the
American Chemical Society under the titles, “Camphonolic Acid and
Camphonololactone,” Vol. XXXIV, pp. 62–67, and “Campholytic Acid
and Related Compounds, Walden Inversion,” Vol. XXXIV, pp. 1067–
Io8O. In 1911 he received the degree of Master of Science from the
University of Illinois.
The writer is a member of the Gamma Alpha Scientific Fraternity, of
Sigma Xi, of the Alpha Chi Sigma and Phi Lambda Upsilon Chemical
Fraternities, and of the American Chemical Society.
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