New Analog of Cupferron R. E. OESPER
AND
R. E. FULMERl
University of Cincinnati, Cincinnati, Ohio
An analog of cupferron containing the fluorene nucleus has been prepared. The new reagent forms precipitates with several metal ions and has been used successfully in the quantitative determination of iron. The noninterference of various metal ions in the iron determination is reported. This fluorene analog has many characteristics in common with cupferron, and is at least as sensitive as neocupferronin the determination of iron.
S
IXCE Baudisch introduced cupferron(1) in 1909 ( I ) , and neocupferron(I1) in 1911 (b), there has been no report of the preparation and analytical evaluation of a cupferron analog containing an aromatic nucleus larger than the naphthyl radical.
N
4
N=O
b--ONH4 I
I
I
N-ONH4 I
I1
I11
The preparation and characterization of the 2-fluorenyl analog of cupferron(III), its employment in the quantitative determination of iron, and its reaction with various metal ions to form precipitates are reported in this paper. EXPERIMENTAL PROCEDURE
Preparation of 2-Fluorenyl Analog of Cupferron. A 500-ml. three-necked flask was fitted with a Hirsch stirrer, thermometer, and gas inlet and outlet tubes so that the reaction could be carried out in an atmosphere of nitrogen. A mixture of 6.0 grams (0.028 mole) of 2-nitrofluorene (4), 6.0 grams (0.11 mole) of ammonium chloride, 25 ml. of water, and 700 ml. of ether was
Table I.
Qualitative Characteristics of Fluorene Analog of Cupferron
Metal Ion Sb++' B ia+++++ Cd++ Ca++ Cr+++
co
Solution Acid (HC1)
1:
++ Pb++ Mn++
+:",
xi++
+$; Th;;
;:++*+ Zn++
+
t
Neutral S1. acid (HCI) S1. acid (HC1) Neutral SI.acid (HCI) Neutral Neutral h-eu t ral Neutral Neutral S1. acid (HC1)
Precipitate Light yellow White White White White Dirty-ahite Red-brown Dirty-white Red-broxn White Dirty-white White White Yellow-green White White White White White White
solution was saturated with ammonia gas and 8.0 ml. ( i . 5 graniu, 0.073 mole) of dried, undistilled n-butyl nitrite (3) were added. The solid product, which formed in about 10 seconds, was allo~r-ed to settle in the cold, was removed by filtration, \\-ashed with cold ether, and dried in air. The light buff crystalline product weighed 2.60 grams (38% yield), Recrystallization from ammoniacal methanol solution, by the addition of ether and cooling, gave a colorless powder that melted a t 201" to 202" C. with much decomposition. Analyses, calculated for C13HgN(KO)OSH4: ammonia, 7.0%; carbon, 64.17y0; hydrogen, 5.39%. Found: ammonia, 6.6, 6.7%; carbon, 64.04%; hydrogen, 5.44%. The ammonia determination was carried out by titration of the compound in 2% boric acid, using standard hydrochloric acid. The indicator used was a methyl red-bromcresol green mixture. Preparation of Ferric Complex of Fluorene Analog of Cupferron. A saturated methanol solution of the reagent was added to an aqueous solution of ferric chloride until no further precipitation was observed. The red-brown product was separated by filtration, extracted into chloroform, and reprecipitated by the addition of ligroine (boiling point, 40" to 60" C.). The darkbrown product did not melt below 280" C. Analyses, calculated for [C13H,N(NO)O]aFe: nitrogen, 115 % ; iron, 7.64%. Found: nitrogen (Dumas) 11.2, 11.1%: iron, 7.41, 7.22%. AR'ALYTICAL PROCEDURES
The fluorene analog of cupferron forms Precipitates with various metal ions (Table I). The ferric, antimony, cobalt, and lead precipitates are readily soluble in chloroform. A saturated methanol solution of the fluorene analog of cupferron was tested as a quantitative precipitant for iron (Table 11),using the procedure described for neocupferron ( 5 ) . DISCUSSION OF RESULTS
Satisfactory values are obtained in the quantitative deterniination of iron when precipitations are carried out in solutions con-
Table 11. Quantitative Determination of Iron Weight of Iron in Test Soln., Mg.
10 10
p
1 Present address, Lederle Laboratories Division, .iinrrican Cyanaiiiid Co., Pearl River, S . Y.
a b
Metal Salt Added
Weight of Salt Added,
5.0 ........... 20.0 ......... 20.0 . . . . . . . . 6.0 . . . . . . . . . 6.0 10.0 10.0 10.0 10.0 10.0 11.0 11.0 10.0 10 0 . . . . . . . . . . . 10.0 CuSOa. 5 H2O 10 0 CuSOi.5 Hn0 10.0 -45203 10 0 Volume o i test .solution 1000 nil. Precipitate washed witii 20 1111. of 6 .V SHaOH.
5
introduced into the flask, which was then swept out Kith nitrogen for 15 minutes. The mixture, kept a t about 20" C. (in a water bath), was agitated vigorously while 15.0 grams (0.20 mole) of zinc dust were added over a eriod of 10 minutes, and the stirring was then continued for an adhitional 10 minutes or until the mixture became yellow and cloudy. The reaction mixture m-as then cooled to '5 C. in an ice bath and allowed to settle. The clear, vellow supernatant liquid was expelled through the outlet tube by nitrogen pressure and passed through a cotton filtei into a 500-ml. flask that had been sn-ept out x i t h nitrogen. The cold
Acid Present HC1 HC1 H~SOI HnSO, Acetic Acetic HC1
Acid Concentration, % by Volume
Mg.
Weight of Ignited Residue Exwessed as hfg. of Iron
3 9 5.3
4.9 5.1
10 140 132 139
226 211
103 276
245
. .
13 24
10
V O L U M E 25, NO. 6, J U N E 1 9 5 3
909
taining hydrochloric acid or acetic acid, but sulfuric acid, in the concentrations used, prevented complete precipitation. The iron in a solution containing as little as 5 p.p.m. can be ~uccessfullydetermined by means of the new reagent. While neocupferron has been employed in the analysis of iron in solutions of the same order of dilution ( 5 ) ,cupferron would not be useful a t such low iron concentrations. The presence of relatively large concentrations of calcium, manganese, nickel, cobalt, zinc, chromium, mercurous, aluminum, cadmium, or trivalent arsenic ions does not interfere with the quantitative iron determination as carried out in solutions containing 6 to 10% (by volume) of hydrochloric acid. The presence of copper in a concentration higher than that of the iron does interfere, even if the precipitate is washed q-ith 6 ammonium hydroxide ( 5 ) .
This new reagent exhibits many of the characteristics of cupferron, but is much more sensitive in the determination of iron
(6). LITERATURE CITED
Baudisch, O., Chem. Ztg., 33, 1298 (1909). Baudisch, O.,Ibid., 35,1141 (1911). Noyes, W.A., Jr., “Organic Syntheses,” Collective Vol. 11, 2n$ ed., p. 108, New York, John Wiley & Sons, 1944. (4) Schulman, S., O T ~Chem., . 14,385 (1949). (5) Smith, G.F., Cupferron and Xeocupferron,” pp. 17-20, Columbus, Ohio, G. Frederick Smith Chemical Co., 1938.
i.
RECEIVED for review October 7, 1952. Accepted March 20, 1953. A portion of a thesis submitted b y R. E. Fulmer in partial fulfillment of the requirements for the degree of doctor of philosophy, Department of Chernist r y , University of Cincinnati, June 1952.
Quantitative Estimation of Amine-Cadmium Halide Complexes By Titration in Nonaqueous Solvents LEO LEV1 AM) CHARLES G. FARMILO Food and Drug Laboratories, Department of National Health and Welfare, Ottawa, Canada
No generally applicable titrimetric procedure for the quantitative estimation of amine-cadmium halide complexes has as yet been reported. It is the purpose of this paper to describe a method which permits such determinations. The complexes are dissolved or suspended in a small volume of glacial acetic acid, reacted with excess mercuric acetate and, after being diluted with p-dioxane, are titrated by means of perchloric acid. The experimental data indicate that the neutralization process takes place in accordance with the general scheme: [Organic . Excess CHsCOOH--t base-cadmium halide complex] HdCzHs0z)z -. acetate of organic base Cd(CHaC00)z [HgX1] HCldO -4cetate of organic base Cd(CHBC00)z dioxane perchlorate of organic base Cd(ClO4)z CH&OOH. The method is as accurate as conventional aqueous acid-base titrations and a precision of &O.Sl% is obtained when using crystal violet as the indicator. Complexes of the type studied are frequently prepared by the forensic chemist as microcrystalline amine derivatives and the method described should prove of particular value in the identification and characterization of medicinally important nitrogenous bases.
-
+ + +
T
+
+
+
WENTY-FIVE years ago Conant, Hall, and Werner ( 4 , 5 ,I O ) showed that many organic compounds which exhibit little or no basic properties in water behave as relatively strong bases in glacial acetic acid and can be accurately determined in this solvent by titration with perchloric acid. The pioneer investigations of these workers were followed by intensive theoretical and applied studies of others and as a result nonaqueous titrimetry with perchloric acid has become a widely accepted method for assaying many classes of chemical substances. Strong and weak organic bases ( 1 , 3, 9, 1.4, 19, 21, S I ) , amino alcohols (19), alkylene oxides ( S ) , amino acids and
polypeptides ( I 11, 20, SO), oxazolines (19),tertiary aliphatic and aromatic amines in the presence of primary and secondary amines ( I , 9, 12, 3 2 ) , basic nitrogen compounds in refined aromatic and aliphatic hydrocarbons ( 3 3 ) and in hydrogenated coal oils (SJ), sulfonamides ( S I ), antihistamines (I@, vitamins and related compounds ( 17 , 22, 24), salts of aniinefi, basic heterocyclic nitrogen and quaternary ammonium compounds (1,8, dd), alkali metal salts (15, 16, 21, as), and salts of organic and inorganic acids (2, 3, 19, 21, 23, S I ) have all been determined by titration with perchloric acid in nonaqueous systems. It is the purpose of this paper to show that the method also permits the quantitative estimation of complexes of organic bases with metal halides. Such compounds are of particular interest to the forensic chemist concerned with the identification and characterization of drugs because, under suitable conditions, the complexes are obtained as microcrystalline precipitates whose characteristic habits may readily be recognized and studied under the microscope. REAGENTS AND SOLUTIONS
Perchloric acid 0.05 21‘ in dioxane, prepared by dissolving a p proximately 4.2 ml. of perchloric acid 70 to 72%- A.C.S. grade in 1 liter of dioxane. Standardization against N.B.S. potassium acid phthalate was performed in accordance with the procedure given by Seaman and Allen ( 2 7 ) . Dioxane, British Drug Houses, certified chemical grade. Glacial acetic acid, A.C.S. grade. Mercuric acetate solutions, made up by dissolving 3 and 6 grams, respectively, of mercuric acetate C.P. in 100 ml. of hot glacial acetic acid and allowing to come to room temperature. Crystal violet indicator solution, prepared by dissolving 0.1 gram of dye (Difco Biological Stain Commission approved sample) in 100 ml. of glacial acetic acid. ANALYTICAL PROCEDURES
Amines and Amine Salts. The organic bases were analyzed in accordance with the procedure given by Fritz (9) and the salts m-ere determined by the method of Pifer and Wollish ( 2 2 ) . Metal Halides. These compounds were analyzed following essentially the procedure given by Pifer and Wollish for the titration of inorganic salts ( 2 3 ) . The accurately weighed sample was dissolved in 0.1 ml. of water, 5 ml. of 3% solution of mercuric acetate in glacial acetic acid were added and, after being diluted
