49% Halocarbon 11-21 on Chromosorb P. The authors apparently did not evaluate the quantitative aspects of chromatographic analysis on this column, which is similar to our columns (b) and (d), found by us to be unsuitable.
ACKNOWLEDGMENT The authors are grateful to the 3M Company for the gift of a sample of compound FC-43 (perfluorotributylamine).
LITERATURE CITED (1) (2) (3) (4) (5)
R. C. Kennedy and J. 8.Levy, J. Phys. Chem., 76,3480 (1972). B. Descamps and W. Forst, J. Amer. Chem. SOC.(submitted). F. B. Dudley and G. H. Cady, J. Amer. Chem. SOC., 85, 3375 (1963). P. M. Nutkowitz and G. Vincow, J. Amer. Chem. SOC.,91, 5956 (1969). J. Czarnowski, E. Castellano, and H. J. Schumacher, Z. Phys. Chem. (Frankfurt am Main), 65, 225 (1969).
(6) 8.Descamps and W. Forst, Can. J. Chem. (submitted). (7) J. M. Shreeve and G. H. Cady, lnorg. Syn., 7, 124 (1963). (8)1. Lysyj and p. R. Newton, Ana/. Chem,, 35,go (1963). (9) J. H. Prager and P. G. Thompson, J. Amer. Chem. SOC.,87, 230 (1965). (10) J . J. Kirkland, Anal. Chem., 35, 2003 (1963). (1 1) J. R. Durig and D. W. Wertz, J. Mol. Spectrosc., 25, 467 (1968). (12) W. P. Van Meter and G. H. Cady, J. Amer. Chem. SOC., 82, 6005 (1960). (13) A. G. Nerheim, Anal. Chem., 35, 1640 (1963). (14) W . S. Pappas and J. G. Million, Anal. Chem., 40, 2176 (1068). (15) J. R. Conder. Anal. Chem., 43, 367 (1971). (16) F. A. Hohorst, D. D. DesMarteau, L. R . Anderson, D. E. Gould, and W. 8. Fox, J. Amer. Chem. SOC., 95, 3866 (1973).
RECEIVEDfor review August 24, 1974. Accepted November 8, 1974. Financial support received from the National Research Canada and the Ministry Of Education Of the Province of Quebec is gratefully acknowledged.
Determination of Chloromethyl Methyl Ether and BisChloromethyl Ether in Air at the Part per Billion Level by GasLiquid Chromatography Richard A. Solomon and George J. Kallos Analytical Laboratories, Dow Chemical U.S.A., Midland, MI 48640
The need to measure airborne concentrations of CMME and bis-CME was dictated by the reported toxicological properties of the compounds, particularly bis-CME which is a known carcinogen a t the 100 parts per billion level in air (1-7). At this concentration, the human sensory system cannot detect these compounds. In the interest of personnel safety, analytical procedures are required which have sufficient specificity and are sensitive to less than 1 ppb. Gas chromatographic-mass spectrometric procedures (8, 9) have been shown to meet both the specificity and sensitivity requirements for the analysis. However, the technique requires sophisticated instrumentation that does not lend itself conveniently to on-site plant analysis. Therefore, gas chromatographic approaches have been studied in an attempt to develop ,a procedure that would be applicable to the on-site monitoring of environmental air. The use of derivatives in gas chromatography as a means of improving analyses is a common practice (10, 11). A novel derivative procedure is described which stabilizes CMME and bis-CME while significantly increasing the detector sensitivity; thus enabling the detection of these compounds a t the part per billion level. High sensitivity is required since 1 v ppb corresponds to 3.3 ng/l. and 4.7 ng/l. of air for CMME and bis-CME, respectively, as calculated from the Ideal Gas Law.
.EXPERIMENTAL R e a g e n t s . Sodium methoxide, AR grade, was obtained from t h e
J. T. Baker Chemical Co., Phillipsburg, N.J. 2.4,6-Trichlorophenol, m p 67-68 "C, was obtained from t h e Eastman Kodak Co.. Rochester, NY. Methanol a n d hexane, distilled in glass, were obtained from Burdick &- Jackson Laboratories, Muskegon, MI. Chloromethyl methyl ether, b p 55-58 'C, was obtained from t h e Eastman Kodak Co., Rochester, NY. His-chloromethyl ether, b p 100-102 "C, was obtained from t h e Eastman Kodak Co., Rochester. NY. Sodium hydroxide, Baker analyzed reagent was obtained from t h e J . T. Baker Chemical Co., Phillipsburg, N J . P r e p a r a t i o n of D e r i v a t i v e R e a g e n t . Twenty-five grams of sodium methoxide were weighed into a beaker a n d dissolved in l
liter of methanol. Five grams of 2,4,6-trichlorophenol were weighed into the beaker and allowed t o dissolve in t h e methanol-sodium methoxide solution. T h e reagent is stable for three t o four weeks when stored in a dark brown bottle. A p p a r a t u s . A Pye Model 104 (Phillips Electronic Co.) gas chromatograph equipped with a 63Ni electron capture detector was used for t h e analysis. I n addition, a series 1400 (Varian) and 5i00A (Hewlett-Packard) gas chromatographs equipped with 63Ni electron capture detector have been successfully used during t h e course of this work. Air samples were collected using glass impingers containing a methanolic solution of t h e sodium salt of 2,4,6-trichlorophenoI. T h e impinger assembly diagram is shown in Figure 1. C h r o m a t o g r a p h i c Conditions. T h e columns used were six feet in length, constructed of %-inch glass tubing and packed with 100/120 mesh textured glass beads (GLC 100) coated with a twocomponent stationary phase consisting of 0.1% by weight QF-1 and 0.1% by weight OV-17. T h e columns were equipped for on-column injection. T h e flow rate of t h e prepurified nitrogen carrier gas was 30 ml/minute. T h e temperature of the sample injection zone was 175 O C and t h a t of the detector was 250 "C. T h e column oven was operated isothermally a t 140 "C. T h e columns were preconditioned a t 170 "C for 4 hours before being connected with t h e electron capture detector. C a l i b r a t i o n . Because of the high toxicity of bis-CME (carcinogenic) and the irritational properties of C M M E to the eyes a n d respiratory system, standards were prepared in a well ventilated hood by dissolving t h e compounds in a given volume of hexane using a microliter syringe. Two pl of C M M E a n d bis-CME were added to 50 ml of hexane. T h e weights of t h e components were obtained by using their respective specific gravities, 1.03 g/ml for CMME and 1.33 g/ml for bis-CME. This concentrated standard was then used for preparing a standard curve. Five milliliters of t h e derivatizing reagent were pipetted into five 10-dram Kimble screw cap vials. T e n , 5, 2, 1, and 0 ~1 of t h e concentrated standard were added. These volumes are equivalent t o 0.50, 0.25, 0.10, and 0.05 pg of bis-CME and 0.40, 0.20, 0.08, and 0.04 pg of C M M E . T h e vials were capped loosely and were placed on a steam bath for 5 minutes. T h e standards were cooled and 5 ml of water and 2 ml of hexane were pipetted into t h e vials. T h e standards were shaken for 5 minutes. Two microliters of t h e hexane extract were taken for chromatographic analysis. A chromatogram of t h e standard is shown in Figure 2. Linearity of t h e standards is shown in Table I. P r o c e d u r e s . T e n ml of derivative reagent were added t o t h e impinger (Figure 1).T h e air flow rate was adjusted to 0.5 l./min, a n d ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, M A Y 1975
955
Air Flow
Table I. Linearity of CMME and Bis-CME Standardsa Standard,
Response (mm)
u g l 2 m l hexane Pump
-
0.04 0.08 0.20 0.40 0.05 0.1 0 0.25 0.50 a
AttB
Y
102
* * * * *
10 1 20 2 50 j; 5 100 10 20 2 40 i- 4 86 9 220 22
CMME CMME CMME CMME bis-CME bis -CME bis -CME bis -C ME
*
Sample size, 2.0 pl.
Table 11. Recovery of CMME and bis-CME from Prepared Air Standards CMME,
Run
Figure 1. Air impinger assembly
1
Added
Found
...
...
... ... ...
2 3 4 5 6 7 8 9 10
bisS.ME, u g
pg
Rec.
... ... ... ...
*..
...
... ... ...
...
0.50 0.50 0.50 0.50 0.50
0.46 0.46 0.46 0.46 0.46
92 92 92 92 92
Added
Found
Rec.
2.44 2.48 2.26 0.27 0.13 0.65 0.65 0.65 0.65 0.65
2.12 2.12 2.00 0.27 0.15 0.60 0.60 0.56 0.60 0.58
87 86 89 100 115 92 92 86 92 89
~
CMME Derivative BIS-CME Derivative
where A = response for the component of interest in the sample. B = attenuation of the sample component. C = w t of CMME or bisCME in the standard expressed in nanograms. D = response for the component of interest in the standard. E = attenuation of the standard component. F = volume of sample expressed in liters. v ppb = parts per billion by volume. H = ng/l./ppb (CMME-3.3 ng; bis-CME-4.7 ng).
RESULTS AND DISCUSSION
3
6 Time (min
Figure 2. Gas chromatogram for standard CMME and bis-CME deriv-
ative Column: 0.1% OF-1 and 0.1% OV-17 on 100/120 GLC-100, 6-R X 'A-in. glass column. Column temp.: 140 'C. Flow rate: 30 ml/min N1, Sample size: 2 pI containing 0.08 ng CMME derivative and 0.1 ng bis-CME derivative
a sample equivalent to 1-10 1. of air was scrubbed through the solution. The solution was then transferred to a 10-dram vial. A small amount of methanol was added to rinse the impinger. This was added to the vial. The sample was heated for 5 minutes on the steam bath and then allowed to cool. Five ml of water and 2 ml of hexane were pipetted into the vial. T h e sample was shaken for 5 minutes and 2 pl of the hexane were used to obtain the chromatogram. Calculation
Component (v ppb) = 956
A x B x C D x E X F x H
ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, MAY 1975
Several gas chromatographic approaches were studied in an attempt to develop a procedure that would have sufficient sensitivity to determine CMME and bis-CME a t the part per billion level. The direct determination of CMME and bis-CME using an electron capture detector indicated that this type of detector is not sufficiently sensitive to these compounds to be applicable at the low concentration of interest. An alternate approach involved the concentration of the compounds present in air by absorption on a short Chromosorb 101 column. The components were then eluted onto the analytical column by heating the short column and determined using a hydrogen flame ionization detector. This procedure proved unsuitable because of the inadequate sensitivity of the detector and interferences from trace organics. The possibility of forming stable chlorinated derivatives with CMME and bis-CME was considered because of the highly reactive nature of the compounds. Initial attempts to form derivatives with sodium pentachlorophenate were successful as shown by NMR and IR analysis. However, decomposition of the derivatives was observed during the chromatographic run. Tests with lower chlorinated phenolic compounds indicated that derivatives could be formed with salts of most of the chlorophenols. Derivatives were formed with the sodium salt of 2,3,4,6-tetrachlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, and 2,4-dichlorophenol. The sodium salt of 2,4,6-trichlorophenate was
Table 111. Comparative Analyses of Air for the Determination of Bis-Chloromethyl Ether Using the GC Derivative and the GC-Ms Techniques
Table IV. Response for Various Bis-CME Standards Using Optimized Reagent'"
Bis-chloromethyl ether
Standard,
Equivalent from
Response attenuation,
u g / Z m l hexane
5 L v PPb
mm, x 3 2
found,ppb
0.044 0.22 0.44 0.88
~-
Sample
Added, ppb
703 708 729 749 733 701 702 705 715 726 712 721 725 739 743 720 718 710 706 741
25 25 25 25 25 15 15 15 15 15 5 5 5 5 5 5 5 5 5 5
GC-MS
GC
28 27 21 27 29 19 16 16 16 15 8 8 8 7 7 8 7 7 8 7
24 24 24 24 26 15 15 14 15 14 8 6 8 6 6 6 6 6 6 6
chosen for the analysis because the phenol was commerciably available in high purity, the salt reacted easily, and the derivatives were well suited for chromatographic separation and detection by electron capture. Separate derivatives are formed from chloromethyl methyl ether and his-chloromethyl ether, with both products being determined from the same GC chromatogram. The derivatives have been prepared and isolated in milligram quantities for identification by mass spectrometry, GC-mass spectrometry, and nuclear magnetic resonance. Spectral data of the derivatives for CMME and bis-CME have been shown to be consistent with structures I and 11, respectively.
c1&OCH*OCH, c1 I
OCH,OCH,OCH,
Cl&
c1 I1
Samples were taken by scrubbing air a t a rate of 0.5 liter per minute through impingers containing the methanolic phenate solution (Figure 1). Two impingers were used in series to ensure the trapping of the compounds. The impinger efficiency was evaluated by the use of gas standards prepared in Saran bags. An average recovery of 90% was obtained for both CMME and bis-CME using gas standards prepared in nitrogen. CMME was retained in the first impinger because of its high reactivity; however, bisCME was found in both impingers with approximately 80% of the total recovery in the first impinger. The recovery data are summarized in Table 11. The known components used in chloromethylation processes do not interfere with the determination of CMME or bis-CME. A chromatographic scan of plant air is normally clean showing only the derivative components when CMME and bis-CME are present and the typical background response from the solvent system. A comparison of the derivative GC procedure and the GC-MS procedure for the determination of bis-CME was made during toxicological testing, where constant atmo-
(1
1.9 9.5 19.0 38.0
8 1 1 40 + 2 90 i: 8 200 f 20
Sample, 1.5 p l .
Table V. Recovery of bis-CME from Prepared Gas Standards (10 1. Nz) Using Optimized Reagent 114 Added
Found
0.054 0.085 0.319 0.347 0.726 0.850
0.044 0.085 0.287 0.312 0.653 0.731
Recovery, YO
82 100 90 90 93 86
spheres of bis-CME were maintained a t 5 , 15, and 25 parts per billion. The data obtained from the two procedures under these carefully controlled conditions were in excellent agreement as shown in Table 111. Further experiments have indicated that the sensitivity can he increased 6- to 8-fold by using stoichiometric quantities of sodium methoxide and 2,4,6-trichlorophenol (16.0 grams of 2,4,6-trichlorophenol and 4.4 grams of sodium methoxide dissolved in 1 liter of methanol). When using this formulation, 2.ON sodium hydroxide was used in place of distilled water prior to the hexane extraction of the derivatives. This was necessary to ensure that free trichlorophenol was not extracted into the hexane layer. The linear response for different concentrations of bis-CME using the optimized reagent is shown in Table IV. The recovery for his-CME using prepared gas standards was 82-100% as shown in Table V. Work for optimizing the reaction condition5 for CMME derivative is in progress.
ACKNOWLEDGMENT We thank E. A. Ault, J. P. Heeschen, W. W. Blaser, G. E. Socha, W. B. Crummett, and L. B. Westover for their contribution to the completion of this work.
LITERATURE CITED (1) B. L. VanDuuren, B. M. Goldschmidt, C. Katz, et al., Arch. Environ. Health, 16, 472 (1968). (2) J. L. Gargus, W. H. Reese, Jr., and H. A. Rutter, Toxicol. Appl., Pharmacol., 15, 92 (1969). (3) K. J. LeJ.lg, H. N. MacFarland. and W. H. Reese, Jr., Arch. Environ. Health, 22, 663 (1971). (4) B. L. VanDuuren, A . Sivak, 8. M. Goldschmidt, C. Katz, and S. Melchionne, J. Nat. Cancer Inst., 43, 481 (1969). (5) B. L. VanDuuren. Ann. N.Y. Acad. of Sci.. 163, 633 (1969). (6) W. G. Figueroa et al., N. Engl. J. Med., 288, 1096 (1973). (7) A . M. Thiess et al., Zentralbl. Arbeltsmed. Arbeitsschutz, 23, 97 (1973). (8) L. Collier, Environ. Sci. Techno/., 6, 930 (1972). (9) L. A. Shadoff, G. J. Kallos, and J. S. Woods, Anal. Chern. 45, 2341 (1973). (10) R . J. Wood, Gas Chrornatogr.. 6 , 94 (1968). (11) E. R. Blakley, Anal. Biochem., 15, 350 (1966).
RECEIVEDfor review December 30, 1974. Accepted February 12, 1975. The present gas chromatographic procedure and variations thereof each including the formation of a derivative of CMME or bis-CME, and apparatus therefor, are the subject of several pending United States patent applications. ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, M A Y 1975
957
