Gas chromatographic analysis of isomeric diamino-toluenes

and its application to the determination of 2,4-diaminotoluene in urine and plasma. Peter D. Unger , Marvin A. Friedman. Journal of Chromatography...
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Table VIII. Aromatic Substituent Effects on Retention; Decrease of Free Energy of Specific Interaction Column: 10 NazS04on acid-washedF-1 alumina, 250” C Substituent UP - AGsipma,cal/mole -CHI -0.17 0 -F +0.06 0 - CI +0.23 -440 - Br 1-0.23 -730

decreased ring electron density and, hence, diminished interaction between adsorbate and adsorbent. If this is the case, the Hammett sigma constant, u p , which is a measure of the decrease in the electronic ring density (I3), should indicate the magnitude of the decreased interaction. This decrease has been evaluated by Equation 4 for the Na2S04column; the results and the sigma constants for the parasubstituted halogens are tabulated in Table VIII. The positive Hammett sigma constant implies that the ring electron density is decreased, which corresponds to the proposed decrease in interaction. The planar aromatic line undoubtedly includes the effect of increasing the ring electron density by successive addition of methyl groups. Hence, the -CH3 substituent lies on the aromatic line and provides (13) E. S. Gould, “Mechanism and Structure in Organic Chemistry,” Holt, Rinehart and Winston, Inc., New York, 1959, p. 221.

the base for reference of the halide substituent effects. The effect of fluoride substitution is too small to measure, and conforms to the small value for the sigma constant. CONCLUSIONS

The data establish that physical adsorption on salt-modified alumina is a composite of nonselective (nonspecific) and specific contributions. The latter is a mixture of selective effects due to the pi-character of the adsorbate, its planarity, its substituents (if aromatic), and its cis-trans geometry (if olefinic). Specific salt effects have not been established, but are the subject of additional studies. Gas-solid chromatography provides a convenient means for the study of adsorption in terms of adsorbent, adsorbate, and inorganic salt-pi electron interactions. The approach, as outlined, should provide a convenient means for the study of molecular structure, the pi-character of organic molecules, and the electronic effects of aromatic ring substituents. From an analytical view, GSC with modified alumina adsorbents provides selective separation of cis and trans isomers and of mixtures containing paraffinic, olefinic, and aromatic hydrocarbons with similar boiling points. RECEIVED for review June 8, 1967. Accepted October 11, 1967. Work supported by the U. S. Atomic Energy Commission under Contract No. AT(l1-1)-34, Project No. 45. We also are grateful to the Public Health Service for an Environmental Sciences Predoctoral Fellowship to D.J.B.

Gas Chromatographic Analysis of Isomeric Diami notoluenes L. E. Brydia’ and Friso Willeboordse Chemicals and P h t i c s , Union Carbide Corp., South Charleston, W. Vu. 25303 A gas chromatographic method has been developed for the determination of the isomers of diaminotoluene. The method consists of reacting the diaminotoluene isomer mixture with trifluoroacetic anhydride to form the corresponding diamides. The diamides are then analyzed using one of two procedures. Procedure A i s a simple and rapid method for the quantitative determination of the diaminotoluene isomers but does not resolve the 2,4- and 2,5-isomer derivatives. This is not a serious limitation for analysis of diaminotoluenes produced by the direct nitration of toluene since the 2,5-isomer is normally present only in trace amounts. Procedure A thus serves as an excellent method for quality control of plant-grade material. Procedure B resolves all five isomers normally present in crude diaminotoluene. However, the procedure is slightly longer than Procedure A because of an evaporation step and longer retention times.

DIAMINOTOLUENES have established significant importance as chemical intermediates because they are basic ingredients in the manufacture of polyurethane foams and elastomers. Production of these materials usually begins with the direct nitration of toluene to produce a mixture of isomeric dinitrotoluenes. The dinitrotoluenes are hydrogenated to the corresponding diaminotoluenes, also called tolylenediamines Present address, Chemicals and Plastics, Union Carbide Corp., Bound Brook. N. J. 08805 1



(TDA), which are then phosgenated to toluene diisocyanates (TDI). The toluene diisocyanates are reacted with an active hydrogen-containing polyfunctional molecule, usually a polyol, to foim the urethane. An accurate determination of the positional isomers of the intermediate diamines is important. The ortho isomers (2,3- and 3,4-) are not phosgenated to the corresponding diisocyanates, but form undesirable ureas, and therefore lower the overall efficiency of the TDA-TDI process. It is also desirable to know the relative concentration of the meta isomers (2,4- and 2,6-) since they affect the process exotherm conditions and the ultimate physical properties of the polyurethane. Despite the importance of the isomer content of diaminotoluenes, no suitable, single method for this determination has been reported. The existing methods for this determination have recently been summarized by Mathias, who used NMR for this purpose ( I ) . The NMR method is based on the slight separation of the methyl proton resonances of the TDA isomers in deuterated chloroform solution. This method lacks sensitivity to minor components and gives relatively poor accuracy. An infrared spectrophotometric method (2), specifically developed to determine the 2,4- and 2,6-isomer content of a binary mixture, also lacks sensitivity (1) A. Mathias, ANAL.CHEM., 38, 1931 (1966). (2) A. I. Finkel’shtein and E. N. Boitsov, Zacodsk. Lab., 26, 959



Table I. Instrument Parameters and Relative Retentions of N-Trifluoroacetyl Derivatives of Diaminotoluene Isomers Instrument parameters Procedure B

Procedure A F & M Model 810 gas chromatograph 3 ft x 0.25-inch 0.d.; aluminum tubing packed with 2.0 % neopentylglycol succinate on Chromosorb G

Instrument Column Bridge current Injection port temperature Block temperature Oven temperature Helium flow Sample size

(60-80 mesh) 150 mA 325" C 330" C

200" C (isothermal) 80 ml/min 10 pl of sample solution

F & M Model 5750 gas chromatograph 12 ft X 0.25-inch 0.d.; aluminum tubing packed

with 5.0% OS-138 six-ring m-polyphenyl ether on Chromosorb G, AW-DMCS (100-120 mesh) 180 mA 250" C 275" C 225" C (isothermal) 70 ml/min 5 pl of sample solution

Relative Retentions

Isomer 0.387 0.465 1.00 1.25 1.28


and the presence of ortho isomers leads to erratic results. No gas chromatographic method for the determination of toluenediamine isomers was found in the literature. A direct procedure has been in use in these laboratories for several years (3); however, the method does not separate the two ortho or two meta isomers, but only provides a measure of the total ortho and total meta content of the sample. Determination of amino acids (4-8), amines (9-11), and aminoalcohols (12) by gas chromatography after converting them to trifluoroacetyl derivatives is well known. This paper describes the determination of the isomer content of diaminotoluenes by gas chromatography of their N-trifluoroacetyl derivatives. Primary emphasis in this study was placed on the determination of the 2,4- and 2,6-isomers and their mixture in plant grade material. Common diaminotoluene before phosgenation consists of about 79 2,4-, 20 % 2,6-, less than 0.8 of total 2,3- and 3,4-, and a trace of 2,5-isomer. The 3 3 isomer does not occur in the phosgenation mixture because of the ortho,para orientation effect in the nitration of toluene (13). The compound is not commercially available and, t o our knowledge, has not been prepared. Therefore, the 3,5isomer was not considered in this study.

0.524 0.623 1.oo 1.13 1.25


(3) A. M. Agree and F. E. Critchfield, Technical Center, Union

Carbide Corp., South Charleston, W. Va., unpublished work, 1964. (4) W. H. Lamkin and C. W. Gehrke, ANAL.CHEM.,37, 383 (1965). (5) P. A. Cruickshank and J. C. Sheehan, Ibid., 36,1191 (1964). (6) K. Blau and A. Darbre, J . Chromatog., 17,445 (1965). (7) C. Zomzely, G. Marco, and E. Emery, ANAL.CHEM., 34, 1414 (1962). (8) W. J. A. Vanden Heuvel, W. L. Gardiner, and E. C. Homing, Ibid.. 36,1550 (1964). (9) R. A. Morrissette and W. E. Link, J . Gas Chromatog., 3, 67 (1965). (10) W. H. McCurdy, Jr., and R. W. Reiser, ANAL.CHEM.,38, 795 (1966). (11) R.A.Dove,Ibid.,39,1188(1967). (12) L. E. Brydia and H. E. Persinger, Ibid., 39, 1318 (1967). (13) P. B. D. de la Mare and J. H. Ridd, "Aromatic Substitution; Nitration and Halogenation," Academic Press, New York, 1959, pp. 87-8, 106.













Figure 1. Chromatogram of trifluoroacetyl derivatives of diaminotoluene isomers. Procedure A EXPERIMENTAL

Apparatus. F & M Models 810 and 5750 gas chromatographs equipped with dual columns and thermal conductivity detector were used. The detectors were equipped with W-2 filaments. Detailed instrument parameters are summarized in Table I. Chemicals. Trifluoroacetic anhydride and trifluoroacetic acid were obtained from Eastman Kodak or Matheson Coleman and Bell. The 2,6-diaminotoluene was obtained from K and K Laboratories, Inc., and the 2,4-diaminotoluene was obtained from Matheson Coleman and Bell. The 3,4diaminotoluene and the 2,5-toluenediamine dihydrochloride were products of Eastman Kodak. The sample of crude diaminotoluene was a product of the Union Carbide Corp. All chemicals were used as received except the 2,5-toluenediamine dihydrochloride which was converted to the free diamine by reaction with an equivalent amount of sodium hydroxide and extracted with ether. Procedure A. Sixty to 100 mg of sample was weighed into a 5-ml serum bottle. One milliliter of trifluoroacetic acid was added, the bottle was stoppered with a rubber septum cap, and VOL 40, NO. 1 , JANUARY 1968

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Table 11. Analysis of Diaminotoluene Isomer Mixtures by Gas Chromatography of Their N-Trifluoroacetyl Derivatives Procedure A Added Determineda 296 3942,42 6 24.8 7.9 68.1 24.0 ... 20.8 ... 79.6 20.4 1.9 2.6 1.6 96.2 2.4 ... 77.7 ... 22.7 77.3 33.0 35.7 32.8 31.5 35.7 3.3 3.6 93.2 3.2 4.1 a All results are averages of two or more devrminations. 3948.0

29467.2 79.2 95.5 22.3 31.3 92.6

Table 111. Precision Study on Gas Chromatographic Procedures for Analysis of TDA Isomers Procedure A Procedure B (synthetic sample) (crude product sample) Wt. Wt 72 (Av, 5 (Av, 7 determinadeterminaIsomer tions) Std dev tions) Std dev



1.07 2.12 35.16

0.72 1.25 17.78 79.86 0.39

0.09 0.09

0.49 0.46



0.04 0.03 0.41 0.45 0.03

the mixture was shaken continually until the sample was completely dissolved ( 5 minutes). A partial vacuum was pulled by evacuating some air from the bottle with a 10-ml hypodermic syringe. The derivatives were then prepared by adding 1 ml of trifluoroacetic anhydride to the bottle with a syringe, The solution was allowed to stand for 15 minutes before 10-pl samples were withdrawn and injected into the gas chromatograph. Procedure B. The derivatives were prepared as in Procedure A except that reagent grade chloroform was substituted for the trifluoroacetic acid. The bis-N-trifluoroacetamide derivatives are insoluble in chloroform and precipitate. After allowing the derivative solution to stand for 15 minutes, the bottle was opened and the solvent, excess reagent, and trifluoroacetic acid were evaporated using a stream of nitrogen. The precipitate was then dissolved in 1 ml of reagent grade acetone. Five-microliter samples were withdrawn from the serum bottle and injected into the gas chromatograph. RESULTS AND DISCUSSION

Trifluoroacetic anhydride reacts with both amino groups of diaminotoluenes according to the following equation :




The diamide reaction products were verified using mass spectrometry. 112





11 0











Figure 2. Chromatogram of trifluoroacetyl derivatives of diaminotoluene isomers. Procedure B Peaks at 4, 6, 7,and 15 minutes are minor, unidentified components Preparation of the derivatives according to Procedure A is simple and requires less than 20 minutes after the sample is dissolved in trifluoroacetic acid. Trifluoroacetic acid was chosen as the solvent because both the diaminotoluenes and the amide derivatives are soluble in this medium, and because it eliminates the addition of another component to the derivative preparation. Other solvents were examined, but, in most cases, failed to dissolve either the sample or the derivatives. The trifluoroacetic acid tails slightly on the column used for Procedure A, but it can be tolerated. A 1:1 milliliter ratio of acid to anhydride was employed for the analysis of samples of approximately 60 to 100 mg. An increase in sensitivity can be gained by using less solvent, but this results in longer sample dissolution times. Figure 1 shows a chromatogram of the N-trifluoroacetamide derivatives of a sample containing the 2,3-, 3,4-, 2,6-, and 2,4-isomers. The derivatives of the 2,4- and 2,5-isomers elute together under the conditions of Procedure A. This is not a serious limitation for analysis of diaminotoluenes produced by the direct nitration of toluene since the 2,5isomer is normally present only in trace amounts. Table I summarizes the instrument parameters and relative retentions pertaining to both procedures. Table I1 lists results obtained by using Procedure A to analyze synthetic mixtures of the 3,4-, 2,4-, and 2,6-isomers. The 2,3-isomer could not be included in these synthetics because the pure material is not commercially available. However, a precision study was made on a sample which contained all four isomers, The results of this study are shown in Table 111. When the concentration of the 2,5-isomer is important, a complete analysis can be realized by using Procedure B. Procedure B requires more total analysis time than Procedure A because of an evaporation step and longer retention times. The evaporation step is necessary because trifluoroacetic acid tails considerably on the m-polyphenyl ether column. Unfortunately, no other suitable solvent was found which could dissolve both the parent compounds and the derivatives. Acetone dissolves both, but it cannot be used because of the possibility of incomplete conversion to the derivatives because acetone reacts with diaminotoluenes to form Schiff bases. Chloroform readily dissolves the amines; however, the amide derivatives are insoluble in this solvent. An evaporation step was incorporated into the procedure because no applicable, single solvent was found. Since an evaporation is required, the trifluoroacetic acid is replaced with the more volatile chloroform. After the derivatives












-----C M l N l l T F S

Figure 3. Chromatogram of trifluoroacetyl derivatives of a commercial sample of crude diaminotoluene. Procedure B

-Thermal conductivity detector



Hydrogen flame detector trifluoroacetic anhydride = trifluoroacetic acid


Figure 2 shows a chromatogram of the trifluoroacetamide derivatives of all five TDA isomers, exhibiting the complete resolution under the conditions of Procedure B. A chromatogram of a sample of crude diaminotoluene is shown as Figure 3. Crude TDA is the amine isomer composition obtained by hydrogenation of the dinitrotoluene isomers mixture, and contains considerably more of the ortho isomers (total about 273. It is then refined to yield less than 0.8z of total 2,3- and 3,CTDA before the industrial phosgenation step occurs. The 2,5-isomer in crude TDA elutes at the tail end of the major component, 2,4-TDA, which makes the determination of small amounts of 2,5-TDA (less than l/zoothof the major peak) rather difficult. However, a judiciously chosen change in attenuation alleviates this problem as exemplified in Figure 3. The flame ionization detector response appeared to be more sensitive than the thermal conductivity detector response for 2,5-TDA but an investigation of the precision attained with the thermal conductivity detector proved the response to be very satisfactory. The results of this precision study on the analysis of crude TDA following Procedure B are shown in Table 111. ACKNOWLEDGMENT

are formed, the excess trifluoroacetic anhydride, trifluoroacetic acid (reaction product), and chloroform are evaporated with a stream of nitrogen. The precipitate which remains is dissolved in acetone. Formation of Schiff bases is not possible at this point. Portions of the acetone solution are then chromatographed. Care must be taken so that no precipitate is lost during the evaporation step.

The authors express their appreciation to H. E. Persinger and R. L. Meeker for encouragement and helpful discussions during this work.

RECEIVED for review August 16, 1967. Accepted September 29, 1967. 18th Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, March 1967.

Adsorptive Properties of Terephthalic Acid in Relation to Its Use as a Solid Support in Gas Chromatography Hiroshi Miyake, Mitsuyuki Mitooka, and Tadashi Matsumoto Research Center, Maruzen Oil Co., Kaiso-gun, Wakayama,Japan The adsorptive properties of terephthalic acid have been studied in relation to its use as a solid support in gas chromatography. Though uncoated terephthalic acid itself strongly retains polar solutes and produces marked tailing of their peaks, its adsorptive capacity was effectively eliminated by treatment with small amounts of stationary liquids containing hydroxyl groups. Terephthalic acid was found to be a suitable support for the analysis of compounds which form strong hydrogen bonds such as free fatty acids, alcohols, water, etc. These substances were successfully eluted as symmetrical peaks free from tailing.

THE SOLID SUPPORT used in gas chromatography should, ideally, not possess adsorptive properties toward the components of the sample. But this is often not the case, and the supports commonly used for this purpose frequently interact with highly polar substances. These interactions are generally considered responsible for peak tailing during elution of the substances. To remove this undesirable property, several methods of pretreatment of the solid support have been developed. But none of these are completely effective for separating highly polar substances.

Peak tailing of free fatty acids can be reduced fairly well by using nonvolatile acidic substances, such as stearic ( I ) , phosphoric ( 2 ) , or isophthalic acid (3), as an additive to the liquid phase. This admits an interpretation that the additive deactivates the adsorptive sites on the solid support and also prevents dimerization of the fatty acids. We found that peak tailing of monomethyl terephthalate was reduced remarkably by the use of terephthalic acid as an additive to the liquid phase (Reoplex 400) coated on glass beads (4). But in this case, the amount of terephthalic acid required for the elimination of tailing was far in excess of what was expected from its solubility in the Reoplex 400. From this fact we thought that terephthalic acid would act not only as an additive but as a supporting material. This paper discusses the applicability of terephthalic acid as a nonpolar stationary support in gas chromatography and illustrates it by the analysis of polar substances. A. T. James and A. J. P. Martin, Biochem. J.,50,679 (1952). L. D. Metcalfe, Nafure, 188, 142 (1960). J. G . Nickelly, ANAL.CHEM., 36, 2244 (1964). H. Miyake, M. Mitooka, and T. Matsumoto, Research Center, Maruzen Oil Co., Kaiso-gun, Wakayama, Japan, private communication, July 1966.

(1) (2) (3) (4)

VOL 40, NO, 1, JANUARY 1968