Nonaqueous Titration of Malonic Esters HAROLD E. ZAUGG and FLOYD C. GARVEN Abbott laboratories, North Ckicago, 111. ,The amount of diethyl malonate present in mixture with certain substituted malonic esters can be determined by titration with potassium methoxide in dimethylformamide using azo violet indicator. A number of monosubstituted malonic esters can be determined quantitatively in the presence of disubstituted malonic esters by titration with potassium methoxide in ethylenediamine using o-nitroaniline as indicator.
I
N THE stepwise alkylation of diethyl
malonate to produce disubstituted malonic esters used in the manufacture of barbituric acids, incomplete alkylation results in mixtures containing varying amounts of unsubstituted diethyl malonate in the first step and appreciable quantities of the monosubstitution product in the second. Mihen malonic ester is alkylated with a lower alkyl group such as methyl or ethyl, mixtures containing all three possible products are usually obtained. Clearly, a method for the quantitative analysis of these mixtures is desirable. Fritz (3) reported the successful titration of diethyl malonate, alone, with sodium methoxide in dimethylformamide using azo violet indicator. Brown and Eberly (1) showed by deuterium exchange studies that both methylmalonic and phenylmalonic esters are much weaker acids than the parent ester. Pearson (6) found that, in alcohol, diethyl malonate is an acid 50 to 100 times as strong as its monoethyl substituted derivative. Therefore, under proper conditions, diethyl malonate should be titratable in the presence of its monosubstituted derivatives. By substituting potassium methoxide for sodium methoxide in Fritz's (3) procedure, this expectation has been realized in a number of cases. By changing the solvent and indicator to ethylenediamine and o-nitroaniline, respectively, even the much more weakly acidic monoalkylmalonic esters have been titrated with potassium methoxide. REAGENTS A N D SOLUTIONS
Dimethylformamide, technical grade. Ethylenediamine, 95 to 100%. Azo violet, saturated solution of pnitrobenzeneazoresorcinol in benzene. o-Nitroaniline, 0.15 gram dissolved in 100 ml. of benzene. Potassium methoxide, 0.1N solution 1444
ANALYTICAL CHEMISTRY
in benzene-methanol prepared as described by Fritz (2) and standardized with analytical reagent grade benzoic acid. Diethyl malonate, diethyl monoalkylmalonates, and diethyl dialkylmalonates, purified by careful fractional distillation. TITRATION PROCEDURES
A. Diethyl Malonate in Presence of Substituted Malonates. Dimethylformamide (15 to 25 ml.) is treated with 4 to 6 drops of azo violet indicator and the solvent is titrated to neutrality (clear blue color) with the standardized potassium methoxide. This solution is poured into a flask containing a weighed sample of the malonic ester mixture. The resulting solution is again titrated to neutrality. B. Diethyl Monoalkylmalonatesin Presence of Disubstituted Malonic Esters. The procedure is the same as A, except that ethylenediamine is substituted for dimethylformamide and o-nitroaniline indicator for the azo violet. In all cases the percentage of the material being titrated in the mixture is calculated by the formula,
%
=
ml. of titrant X normality x mol. wt. of ester grams of sample x 10
(1)
compared t o 99% with potassium methoxide. o-Nitroaniline as an indicator in this titration also gives low results and very poor end points. Lithium methoxide is completely unsatisfactory as a titrant. This titration becomes less reliable as mixtures containing only a few per cent of diethyl malonate are encountered. Thus, the purest sample of diethyl (1-methylbuty1)malonate obtained gives a 2% blank in Procedure A. This is a true blank and not caused by the actual presence of diethyl malonate, because all other monosubstituted malonic esters examined behave similarly. The effect becomes more pronounced as the size of the substituent decreases. The following blanks were observed in increasing order of magnitude (decreasing bulk of substituent): diethyl sec-butylmalonate, 2.3%; diethyl isopropylmalonate, 4.0%; and diethyl n-butylmalonate, 13%. This effect is probably a reflection of the increase in acid strength of these malonic esters as the structural simplicity of diethyl malonate itself is approached. An explanation of this phenomenon lies in a consideration of the resonance stabilization of the enolate anions of these esters (4). OEt
RESULTS A N D DISCUSSION
Table I summarizes the results obtained by titrating, according to Procedure A, a series of carefully weighed synthetic mixtures of diethyl malonate with diethyl (1-methylbuty1)malonate. Titration according to Procedure A, but using sodium methoxide in place of potassium methoxide, gives low results. Pure diethyl malonate gives a titer of 97% with sodium methoxide as
// R-'2 I
c
OEt
A-0"
R o' m
.t--f
R-C
e/
I
C 0/ \OEt
OEt 1 Ra/
0
Table I. Titration of Diethyl Malonate Alone and in Mixture with Diethyl ( 1 -Methylbutyl)malonate w t . of sample, Diethyl Malonate, yo Gram Present FGZ 0.2066 30.17 30.62 0.2066 39.91 39.32 0.2074 45.06 44.52 0.2010 49 87 49.34 0.1995 54.93 54.00 0.1996 59.98 58.69 0.2044 69.79 68.60 0.1550 100.0 99.0
-
A 4
\
OEt
To obtain maximum resonance stabilization of this system, the four oxygen atoms, the three central carbon atoms, and the atom joining the R group to the rest of the molecule must all lie in the same plane. In diethyl malonate (R = H), this requirement is met easily; but as the R group increases in bulk, particularly in the vicinity of its point of attachment to the central carbon atom, steric requirements gradually supersede. As the coplanar configuration becomes less favored, lowered
stability of the anion results, reflected by a decrease in acidity of the substituted malonic ester. Ethyl cyanoacetate could not be titrated in the presence of its monosubstituted derivatives by Procedure A. If resonance is involved a t all, the anions of cyanoacetic esters would be stabilized by more linear forms,
Table II. Titration of Diethyl (1Methylbutyl)malonate (DMBM) Alone and in Mixture with Diethyl Ethyl( 1 -rnethylbutyl)malonate Wt. of
S a
R
\c/
C
//
Sample, Gram
DMBM, % Present Found
1.00 1.00 1.00 1.00 1.00 0,1004
2.27 5.13 8.27 10.15 12.25 100.
2.27 4.90 8.02 9.84 11.73 98.1
I
0 ’
‘OEt
which would not be subject to as much hindrance by a large R group. If the acidity of cyanoacetic esters is caused largely by inductive effects, then the coplanar requirements of resonance become irrelevant. In either case, the acid weakening effect of substitution would be less apparent in the
cyanoacetic ester series than in the malonic esters. Table I1 summarizes the results obtained by titrating according to Procedure B a series of weighed mixtures of diethyl (1-methylbuty1)malonate with diethyl ethyl( 1-methylbuty1)malonate. Procedure B has been used successfully in analyzing the following mixtures of esters: diethyl (1-methylbutyl) malonate in diethyl allyl(1-methylbutyl)
malonate, diethyl isopropylmalonate in diethyl ethylisopropylmalonate, diethyl sec-butylmalonate in diethyl sec-butylethylmalonate, diethyl n-butylmalonate in diethyl n-butylethylmalonate, diethyl isopentylmalonate in diethyl isopentylethylmalonate, and diethyl phenylmalonate in diethyl ethylphenylmalonate. LITERATURE CITED
W. G.. Eberlv. K.. J . Am. Chem. &c. 62,113 (1940j.‘ ’ (2) Fritz, J. S., “Acid-Base Titrations in Nonaqueous Solvents,” p. 31, G. F. (1) Brown. \-I
~~
Smith Chemical Co.. Columbus, Ohlo,
1952. (3) Fritz, J. S.,ANAL, CHEII. 24, 674 (1952). (4) Hammond, G. S.,in “Steric Effects
in Organic Chemistry,” M. S.Newman, ed., pp. 442-54, Wiley, New York,
1956. (5) Pearson, R. G., J. Am. Chem. SOC. 71, 2212 (1949).
RECEIVED for review January 6, 1958. Accepted March 31,1958.
Nonaqueous Titration of 2,4-Dinitrophenylhydrazones A. J. SENSABAUGH, R. H. CUNDIFF, and
R. J.
P. C. C.
MARKUNAS
Reynolds Tobacco Co., Winston-Salem, N.
b 2,4-Dinitrophenylhydrazones of aldehydes and ketones can be titrated as weak acids with tetrabutylammonium hydroxide. This provides another simple and rapid method for the identification of this important group of carbonyl derivatives.
R
ECENTLY,
Fritz, RiIoye, and Richard
(6) demonstrated that nitroaro-
matic amines can be titrated quantitatively as acids in pyridine with tri-ethyl-n-butylammonium hydroxide. Their study included the potentiometric titfation of nitroaromatic compounds that are acidic yet do not have functional groups that are generally considered acidic. 2,4-Dinitrophenylhydrazine, which contains a basic functional group and can be titrated as a base in glacial acetic acid (IO), was also titrated as an acid with tetrabutglammonium hydroxide in the authors’ laboratory. This suggested that 2,4-dinitrophenylhydrazones should titrate as weak acids and thus afford another simple method for the characterization of this important group of derivatives. The 2,4dinitrophenylhydrazones of aldehydes and ketones have been identified by elemental analysis, melting point, paper chromatography, absorption spectroscopy, and infrared spectroscopy
(2, 9, I S ) . The proposed method should be a useful adjunct to these other means of isolation and identification. By the proposed procedure, samples as small as 1 to 2 mg. can be analyzed with an accuracy of *2%, This was possible by the use of 0.01 to 0.02.47 titrants. Although quaternary ammonium hydroxide titrants have been employed by several investigators ( I , 3-6, 7 , 8 ) , none suggested the use of a titrant weaker than 0.1N. Pifer, Rollish, and Schmall demonstrated the usefulness of titrants as weak as 0.001N in other nonaqueous solvent systems (11, 12). Useful titrants as low as 0.002N can be obtained by diluting 0.01N tetrabutylammonium hydroxide in 10 t o 1 benzene-methanol with additional benzene. The preparation and use of these more dilute titrants will be discussed more completely in a subsequent article; in the present investigation, the dilute titrants are homogeneous and appear stable on standing. As these solutions contain considerably less methanol than the 0.1N titrant, they have proved exceedingly versatile. REAGENTS A N D APPARATUS
Tetrabutylammonium hydroxide, 0.01 and 0.02N. Prepare 0.1N tetrabutyl-
ammonium hydroxide as previously described (4). Dilute 100 and 200 ml. of this 0.1N titrant to 1 liter with benzene. The dilutions contain benzene-methanol ratios of 100 to 1 and 50 to 1, respectively. Standardize each by titration against benzoic acid in pyridine solution. Restandardize as may be required. Pyridine. Allow technical grade pyridine to stand overnight over sodium hydroxide pellets, then flash distill. Precision-Shell Dual AC Titrometer (Precision Scientific Co., Chicago, Ill.) , using the electrodes described previously (3). PROCEDURE
The procedure consisted of dissolving 2 to 20 mg. of the 2,4dinitrophenylhydrazone in 50 ml. of pyridine and titrating potentiometrically in an inert atmosphere, with either 0.01 or 0.02N tetrabutylammonium hydroxide. After correcting for the solvent blank, the end point was determined from a plot of the millivolt readings us. volume of titrant used. EXPERIMENTAL
All of the 2,4-dinitrophenylhydrazones tested titrated as weak acids. The use of indicators was not warranted because of the intense coloration imparted to the solution by the 2,4dinitrophenylhydrazones. VOL. 30, NO. 9, SEPTEMBER 1958
1445
