procedure. Boron \pas quantitatively recovered by this procedure from 5-ml. sample aliquots of concentrated nitric acid. This confirms the study of Feldman (2), in which he evaporated nitric acid samples without loss of boron. Losses will occur if the heating is allowed to continue after the nitric acid is evaporated. Metal Ions. As shown in Table I, of 30 metal ions studied, only five extracted and caused high emission rc.adings a t a mole ratio to boron equal to or less than 1. Most metal ions had no effect a t a 10 to 1 mole ratio and nianv had no effect a t a 100 to 1 ratio. Iron(II1) as a chloride complex and dichromate also extract and cause high emission readings. Hydroxylamine will reduce both these ions to nonevtractable forms and the hydroxylamine does not interfere with
the flame emission of the extracted boron. Several metal ions were added as nitrate salts (as indicated in Table I). In some cases the total nitrate exceeded the noninterference level of about 10 mmoles, causing the observed low flame readings. OTHER APPLICATIONS
The high flame emission readings for some metal ions, particularly Mo(VI), Nb(V), Pt(IV), Ru(III), V(V), and R(VI), are indicative that this system might be useful for their flame photometric determination. The study of a chloride media extraction system also seems promising. The high flame readings observed with platinum and ruthenium are attributed to their eutraction as chloro complexes.
LITERATURE CITED
(1) Dean, J. A., “Flame Photometry,”
McGraw-Hill, New York, 1960.
(2) Feldman, Cyrus, AXAL. CHEM.33,
1916 (1961).
(3) Gilbert, P. T., Beckman Instruments,
Inc., Fullerton, Calif., private communication, November 1960. (4) Maeck, W.J., Booman. G. L., Kussy, M. C., Rein, J. E., ASAL. CHEM.33, 1775 (1961). (5) Morrison, G . H., Freiser, H., “Solvent Extraction in Analytical Chemistry,” Wiley, New York, 1957. (6) Pasztor, L. C., Bode, J. D., ASAL. CHEM.32, 1530 (1960). ( 7 ) Pasztor, L. C., Bode, J. D., Fernando, Quintue, Zbid., 32, 277 (1960). RECEIVED for reviewed August 8, 1962. Accepted October 22, 1962. First Annual Pacific Meeting of Applied Spectroscopy and Analytical Chemistry, Los Angeles, Calif., October 1962. Work done under Contract .4t( 10-1)-205 t o Idaho Operations Office, IT. S. Atomic Energy Commission,
Determination of Benzyl Chloroformate by Gas Chromatography of Its Amide Extension of the Principle to Other Acid Chlorides CHARLES HISHTA and JOSEPH
BOMSTEIN
Brisfol Laborafories, Division o f Brisfol-Myers Co., Syracuse, N.
b A combined chemical and gas chromatographic method has been developed for determining benzyl chloroformate and carboxylic acid chlorides in the presence of carboxylic acids. The method depends on converting the acid chlorides to amides by the use of diethylamine in chloroform, followed by gas chromatographic separation of the amides on glass beads coated with O.25y0 Carbowax 1500. Applied to benzyl chloroformate and to a-phenoxypropionyl chloride, precision is shown to be 1.9 and =t2.4%, respectively (relative standard deviations).
*
I
x SYIiTHESIziNG carboxylic acid chlorides by conventional techniques, such as reaction of a carboxylic acid with thionyl chloride or phosphorus pentachloride, a mixture of the acid chloride, carboxylic acid, and hydrochloric acid generally results. Because these acid chlorides are often expensive and important intermediates, considerable attention has been given to determining them separately and in their mixtures. Lohr ( 2 ) has recently reviewed the work which has been done. Methods which have been applied are titrimetric in nature, either differential
Y.
or direct, and depend on neutralizing the acids present. Lohr’s work (2) involved a direct potentiometric titration of the acid chloride with cyclohexylamine; earlier methods required determination of the acid chlorides by difference. The present study was originally undertaken to provide a method for determining the purity of benzyl chloroformate (abbreviated hereafter as CBZ to conform with the name carbobenzoxy chloride in common usage), which appears to be too unstable to determine accurately by existing methods. The technique developed was found to apply as well to carboxylic acid chlorides, alone and in mixtures. Advantages are freedom from interference by other components, ability to measure the acid chloride directly (as the amide), and minimization of decomposition during analysis. PRINCIPLE
OF THE METHOD
The acid chloride mixture is dissolved in a suitable solvent and allowed t o react with diethylamine. The resulting amide solution is extracted with acid to remove excess amine, and the amide is determined quantitatively by gas chromatography.
Separation of amides by gas chromatography has apparently received scant attention. Saunders and Murray (3) have reported the identification of amides from the reaction of dichlorocarbene with amines, but no detailed studies appear to have been published. Direct determination of the acid chlorides by gas chromatography was attempted in our laboratory, but decomposition of the samples during passage through the column prevented our adopting this approach. PROCEDURES
Procedures described here are for the determination of CBZ, but have been shown to be generally useful, as exemplified by applying them also to other acid chlorides. Preparation of Amide. Approximately 0.015 mole of CBZ is weighed accurately into a 10-ml. volumetric flask and diluted t o volume with Spectro-grade chloroform. A 2-ml. aliquot is pipetted dropwise into a 20-ml. test tube immersed in a n ice bath and containing 2 ml. of chloroform and 2 ml. of diethylamine. The mixture is agitated continually during the addition, and, finally, is stirred for 15 minutes a t room temperature. VOL. 35, NO. 1 , JANUARY 1963
65
The amide solution is extracted once with 10 ml. of 114' hydrochloric acid, then washed twice nith 10 ml. of distilled water. Internal Standard* 0.68 gram of methyl salicylate (analytical reagent grade) is weighed accurately into the amide solution, and 2.5 ml. of ethyl alcohol is added to solubilize the mixture. Gas Chromatography. The F & M Model 500 gas chromatograph is used under the following conditions: Support 100-140 mesh glass beads Substrate 0.257, Carbowax 1500 Column Copper, 18 by inch Detector temp. 275' C. Detector current 150 ma. 1 Attenuation 280' C. Inlet temp. Calculations. Products of peak height b y half width are taken as the measure of peak area, and the usual internal standard calculations are carried out to determine concentration. RESULTS A N D DISCUSSION
Under the conditions chosen, retention times for methyl salicylate and the CBZ amide are 4.4and 9.7 minutes, respectively, and the apparent HETP is approximately 0.012 cm. for the latter.
Table 1. Precision of Combined Preparative and Chromatographic Procedures
Factor F 0.672 0.673 0.680 0.696 0.699 0.708 0.698 0.688 0,699
Sample weight, g. 0.48 0.36 0.27
Precision and Accuracy. The precision of the method was determined by the values obtained for the factor F (ratio of peak area per gram of internal standard t o Peak area Per gram Of using different weights of sample. This measure of precision includes errors due t o sample preparation, weighing, and chromatographic procedures. Table I shows data i n triplicate at three sample levels. Helium flow, column Helium flow, reference Sample size Initial column temD. Program rate Cutout temp.
analyzed immediately upon receipt (day 1) and after 24 hours' storage in a refrigerator (day 2 ) . Carboxylic Acid Chlorides. The general applicability of the techniques described has been demonstrated b y applying them to the determination of three additional acid chlorides of commercial importance t o this laboratory : 2,6-dimethoxybenzoyl chloride (DMBC), a-phenoxypropionyl chloride (PPC), and 3-phenyl-5methyl-4-isoxazolyl chloride (PMIC), Conditions for preparation of the amide were unchanged, but chromatographic conditions were altered to allow for differences in structure, polarity, and molecular weight of the amides involved. Quantitative data were obtained for
36 ml./min. 17 ml./min. 0 . 8 fil. 75" C. 7.9" C./min. 160' C.
In terms of relative standard deviation, the precision for all nine data points is 1.9% and it is clear that F is satisfactorily constant over a range of sample levels. Day-to-day variability has been found to be somewhat greater, but this factor has been minimized by carrying a calibration sample through the analytical procedures along with the unknowns. This precaution is advisable in all cases, because of the possibility of day-to-day changes in instrumental conditions. A high-purity sample purchased from Mann Research Laboratories, and guaranteed t o be better than 99% CBZ, was analyzed by this method. The data of Table I1 show the duplicate results obtained for two different runs on two succeeding days. If the sample is assumed t o be 99.5% CBZ, the relative error of the mean of duplicates is +2.0%. The material was
*
Table
IV.
Precision for Determination of PPC
Sample wt., g. 0.464
Factor F 0.378 0.386 0.389 0.378 0.391 0.387 0.390
0.367
0.400
0.271
0.399 0.371 0.374
Table
V.
Sample 1
2
Accuracy for PPC Gas chrom. Chemical method, 7, method, % 99 97 101 98
r
CDS
1 Table 11.
Sample 1
2
Table 111.
Accuracy of Method
Concentration of CBZ, % Day 1 Day 2 102.8 101.7 102.5 100.2 ... 100.7 101.3 Retention Times and Values
Compound CBZ PPC DMBC PMIC
Retention time, min. 1.8
3.2
6.4
7.8
i
HETP
HETP, cm. 0.25 0.12 0.036 0.026
TIME
Figure
66
0
ANALYTICAL CHEMISTRY
1.
PUIC
DUDC
n
i
-
Chromatogram
of four amides
PPC, but for DMBC and PMIC the final, quantitation step was not carried out. Figure 1 shows an actual chromatogram of all four amides, obtained under the following conditions: Support Substrate Column Detector temp. Detector current Attenuation Inlet temp.
100-140 mesh glass beads 0.25% Carbowax 1500 Copper, 28 by inch 275" C. 195 ma. 1 340" C.
Internal standard was omitted from the chromatogram. The retention times and values of apparent H E T P calculated as though the chromatograms were isothermal are given in Table 111. I t is noteworthy that under these conditions, the high-boiling amides are taken off a t such low temperatures. These range from 145" C. for CBZ to 206" C. for PMIC, and appear to be the result of the choice of column packing, as pointed out initially by Hishta et al. ( I ) . Quantitative data were obtained for PPC, using the conditions described earlier for preparation of the amide, and slightly modified conditions for the subsequent chromatography. Chromatographic changes involved a lengthening of the column to 28 inches, an increase in helium flow to 45 ml. per
minute, and a change of temperature program to 11' C. per minute over an 80" to 190" C. range. Table IV lists replicate data obtained for PPC on the basis shown in Table I for CBZ. Retention times were 4.4 and 9.8 minutes Helium flow, column Helium flow, reference Sample size Initial column temp. Program rate Cutout temp.
125 ml./min. 13 ml./min. 1 pl. 125" C. 11"
c.
205" C.
for internal standard and PPC amide, respectively. The relative standard deviation for all 11 data is =!=2.4%, and F is satisfactorily constant over the range of sample levels chosen. This precision represents the combined chemical and chromatographic steps. Two commercial samples of PPC were analyzed by this technique, and the results were compared with values obtained by the chemical met,hod described by Stone (4). Table V lists the data and shows a relative error of + 2 to 3%. Based on the data presented above, we conclude that a method of general applicability has been developed for determining carboxylic acid chlorides. Although the small concentration of residual carboxylic acid usually present
initially in acid chloride samples is not determined, it is likely that a modification of the procedures would accomplish this too. For example, following the formation of the amides and the extraction of excess amine, the carboxylic acid could be extracted with alkali, estefied, and subjected to gas chromatographic assay. Alternatively, the carboxylic acid could be determined by direct titration in the presence of the amide, and the same sample used for gas chromatography. ACKNOWLEDGMENT
The authors are indebted to J. P. Messerly for his original suggestion of applying gas chromatographic procedures to the determination of acid chlorides, to W. D. Cooke of Cornel1 University for reviewing this work, and t o Bristol Laboratories for permission to publish this paper. LITERATURE CITED (1) Hishta, C., Messerly, J. P., Reschke,
R. F., Fredericks, D. H., Cooke, W. D., ANAL. CHEM.32, 880 (1960). (2) Lohr, L. J., Ibid., 32, 1166 (1960). (3) Sanders, M., Murray, R. W., Tetrahedron 11, 1 (1960). (4)Stone, K. G., "Determination of Organic Compounds," pp. 97-9, McGraw-Hill, New York, 1956. RECEIVEDfor review June 6, 1962. Accepted November 14, 1962.
Determination of Tobacco Humectants by Gas Liquid Chromatography R. L. FRIEDMAN' and W. J. RAAB Technical Service I aboratory, Shell Chemical Co., Union, N.
b A technique is described for the extraction and determination of various humectant polyols added to cigarette tobaccos. Six major cigarette brands were extracted using acetone as solvent. The solution was purified and the acetone was removed under reduced pressure. The residue was then dissolved in methyl alcohol, and the presence of propylene glycol, diethylene glycol, and glycerine was determined b y chromatographic separation.
M
IXTURES
OF VARIOUS
POLYOLS,
namely propylene glycol, diethylene glycol, and glycerine, are used as humectants in the manufacture of cigarettes. A recent literature survey for a suitable technique t o determine humectant composition of cigarettes did not disclose any procedures that were relatively simple and rapid, yet
J.
capable of giving good qualitative and quantitative results. Chemical procedures involving oxidation of alpha glycols and acetylation of total hydroxyl groups gave only fragments of information, and identification of individual compounds was not totally feasible by these techniques. Also, the results from the chemical analyses can be obscured by other tobacco ingredients containing reactive hydroxyl groups. Availability of suitable equipment and successful experience with gas liquid chromatography in other fields caused us to settle on this technique as the basis of an analytical procedure for tobacco humectants. The development of an analytical technique for determination of selected components of a complex mixture usually involves two basic stepssample preparation and the actual analysis. For the analysis of tobacco humectants by GLC, it was apparent
that extraction of the humectants from the cigarette tobaccos would be a necessary first step. The crude tobacco extract would then have to be purified to rid it of gross contaminants that could interfere with or complicate subsequent analysis. Since the procedure developed may represent a step forward in the analysis of glycol-poly01 blends and, consequently, may be of practical value to some segments of the tobacco industry, a detailed description of the entire procedure will be given below. EXPERIMENTAL
Apparatus. The GLC equipment used in this study was a F & M Model 300 programmed gas liquid chromatograph. The chromatograph was fitted with a 6-foot stainless steel 1
Present addreea, Shell Chemical Co.
415 Madison Avenue, New York, N. Y. VOL. 35, NO. 1, JANUARY 1963
67
