Preparation of Trimethysilyl Ethers of Tertiary Alcohols SIR: Trimethylsilyl ethers of alcohols, (6-8, 12) including carbohydrates (10, 11) and sterols, (9) and of phenols (1-4) have been demonstrated to be very useful derivatives for separation, identification, and analysis of the parent hydroxyl compounds. I n particular, these derivatives have been widely used for infrared ( I ) , mass spectrometric (?'), and gas chromatographic analysis (8-11). For such purposes, quantitative preparation of derivatives without formation of side products is desirable. Such procedures exist for trimethylsilyl ether formation of primary and secondary alcohols, and of phenols, including even very highly hindered ones. However, no suitable procedure has been reported previously for tertiary alcohols. While tertiary alcohols will not react with hexamethyldisilazane alone or in petroleum ether to form trimethylsilyl ethers, they will react with trimethylchlorosilane in pyridine (6)* R3COH (CH3)3SiC1 C&5N + R&OSi(CH& Ca5N.HCl
+ +
+
or with hexamethyldisilazane and trimethylchlorosilane in petroleum ether (6, 12).
2RsCOH
+ (CHa)rSiCl
(CH3)aSiNHSi (CH3) --+ 2R3COSi(CH& NH3
+
Yields from these procedures are far from quantitative, and olefins and halides are formed in substantial amounts. Thus, purification can be a problem. Moreover, in both procedures HCl is formed, giving rise to conditions which might be conducive to rearrangements. The situation is further complicated in the case of an olefinic tertiary alcohol, which might be expected to react with HC1 formed in the reaction of the alcohol and trimethylchlorosilane. One solution to this problem appeared to be the use of hexamethyldisilazane in dimethylformamide, which has been found to be an effective agent for converting hindered phenols to their trimethylsilyl ethers ( 2 ) . EXPERIMENTAL
Reaction of
2-Methyl-2-Butanol
with Hexamethyldisilazane in Di-
methylformamide. A solution of 10 ml. of 2-methyl-2-butanol (purity checked by gas chromatography), 15 ml. of hexamethyldisilazane, and 50 ml. of freshly distilled dimethylformamide was refluxed overnight. Gas chromatographic analysis of the resulting red solution showed some unreacted hexamethyldisilazane. Because 144
ANALYTICAL CHEMISTRY
-
the trimethylsilyl ether [boiling point 130" C. (6)]boils only a few degrees above hexamethyldisilazane, it was necessary to destroy the excess reagent by adding tridecanol and refluxing for two hours. The solution was then distilled through a 40-cm. vacuum jacketed packed column. The distillate was analyzed by gas chromatography on a 12-foot by l/S-inch i.d. column packed with Apiezon on Chromosorb P operated a t 65" C. and inlet pressure of 27.5 p.s.i.g. of helium. I n addition to the expected trimethylsilyl ether, traces of several other compounds were found. Mass spectral analysis of the trimethylsilyl ether verified the molecular weight as 160. Infrared analysis showed the expected trimethylsilyl ether bands, and in addition, a carbonyl band believed due to an impurity. Reaction of 2-Methyl-2-Butanol and Hexamethyldisilazane in Dimethylsulfoxide. A solution of 20 ml. of 2-methyl-2-butano1, 30 ml. of hexamethyldisilazane, and 50 ml. of dimethylsulfoxide was refluxed overnight. During refluxing, two phases separated. The upper phase was essentially pure 2-trimethylsiloxy-2-methylbutane. This phase was distilled, and the distillate analyzed by infrared and nuclear magnetic resonance. The infrared showed the expected trimethylsilyl ether bands, and no hydroxyl or carbonyl absorption. The nuclear magnetic resonance spectrum was identical to the spectrum of 2-methyl-2-butano1, with the substitution of trimethylsilyl protons for the hydroxyl proton. Gas chromatographic analysis of the lower phase showed only a trace of alcohol, and no other compounds derived from it. By a similar procedure, 3-trimethylsiloxy-3-ethylpentane (boiling point 1701" C.) and 2-trimethylsiloxy-2-propyl-4methylpentane (boiling point 174-6' C.) were prepared. Hydrolysis of 2-Trimethylsiloxy-2Propyl-4-Methylpentane. A solution of 1 ml. of 2-trimethylsiloxy-2-propyl4-methylpentane, 10 ml. pyridine, 1 ml. of water, and 2 drops of concentrated hydrochloric acid was refluxed for 2 hours. The solution was diluted with 150 ml. of water and the organic layer was separated and analyzed by gas chromatography. Hydrolysis was complete. Only nonisomerized alcohol was found. Hydrolysis of 1 ml. of the trimethylsilyl ether in a solution of 2 drops of concentrated hydrochloric acid in 11 ml. of 85% ethanol was complete after 42 minutes of refluxing ( I ) . However, gas chromatographic examination of the product indicated that dehydration and isomerization had taken place. Further refluxing led to more isomerization of the alcohol. No reaction was observed when hydrolysis was attempted in 85% ethanol, aqueous pyridine, aqueous ethanol-pyridine, and aqueous ethanol-
pyridine containing a trace of glacial acetic; methanol containing a trace of hydrochloric acid (2) caused extensive reaction but no alcohol was identified among the products. RESULTS AND DISCUSSION
For exploratory experiments to check the use of dimethylformamide, 2methyl-2-butanol was chosen as an example of a tertiary alcohol. While the reaction between 2-methyl-2-butanol and hexamethyldisilazane in dimethylformamide did proceed to give very good conversion to the trimethylsilyl ether, a secondary product was formed which could not be readily separated from the ether by distillation. This compound was apparently formed from the dimethylformamide and the hexamethyldisilazane, although it was not separated and identified. The same material is formed (in small amounts) by refluxing dimethylformamide and hexamethyldisilazane. This procedure should be useful for tertiary alcohols which boil higher than 2-methyl-2-butano1, thus allowing the impurity to be removed by distillation. Gas chromatography of the reaction mixture indicated that no alcohol remained unreacted, and no other products were formed. Infrared, mass spectral, and nuclear magnetic resonance analysis of the trimethylsilyl ether confirmed the identity of the product. The similarity between the nuclear magnetic resonance spectra of the alcohol and the ether indicated that rearrangement had not taken place. The reason for choosing dimethylformamide initially was its good solubilizing characteristics and its high dielectric constant ( 2 ) , two properties which make it an excellent medium for many ionic reactions. Another solvent which shows equally good characteristics is dimethylsulfoxide, which has recently become readily available. I n an effort to overcome the difficulties encountered with dimethylformamide, dimethylsulfoxide was substituted as a solvent. This proved to be an unexpectedly good reaction medium, for not only does the formation of the trimethylsilyl ether proceed to completion rapidly, but the product is insoluble in dimethylsulfoxide and separates as a distinct layer, thus aiding isolation of the product. In addition, any excess solvent is easily removed by washing with water. Using this procedure, the trimethylsilyl ethers of 2-methyl-2-butanol, 3ethyl-3-pentanol ,and 2-propyl-4-methyl2-pentanol have been prepared in quantitative yield.
Quantitative hydrolysis of the trimethylsilyl ethers was accomplished by refluxing in pyridine containing an excess of water and 2 to 3 drops of hydrochloric acid. The alcohol was then recovered by distillation. The alcohol was identical to the starting alcohol, as shown by infrared analysis. The use of diniethylsulfoxide as a solvent for preparing trimethylsilyl ethers of hydroxyl compounds other than tertiary alcohols may be indicated in cases where the compound, such as a carbohydrate, is insoluble in pyridine and in hexamethyldisilazane, or when the presence of double bonds requires the absence of a n acid catalyst, as is the case for certain steroids and terpenes. The lack of solubility of the ethers in dimethylsulfoxide should also be of use in cases where ease of separation is important. One further application of the selectivity of reaction shown by various solvents in trimethylsilyl ether formation is in distinguishing between primary, secondary, and tertiary alcohols. Primary and secondary alcohols are converted to trimethylsilyl ethers by refluxing with hexamethyldisilazane ( 6 ) , but the tertiary alcohols require the
presence of dimethylformamide or dimethyl sulfoxide. When a mixture of 1-pentanol, 3-pentanol, and 2-methyl-2butanol was refluxed with hexamethyldisilazane, only the primary and secondary alcohols formed trimethylsilyl ethers as observed by gas chromatography. Addition of dimethylsulfoxide resulted in conversion of all three alcohols. In this way, tertiary alcohols can be distinguished from primary and secondary alcohols in a mixture, even when nonalcohol constituents are present. ACKNOWLEDGMENT
The authors thank Herbert Retcofsky for his assistance in running and interpreting the N M R spectra. LITERATURE CITED
(1) Friedman,
S., Kaufman, 31. L., Steiner, W. A., Wender, I., Fuel (London) 40, 33 (1961). (2) Friedman, S., Kaufman, M. L., Wender, I., J . Org. Chem. 27, 664 (1960). (3) Friedman, S., Steiner, W. A., Raymond, R., Wender, I., Preprints of Gas and Fuel Division, 132nd Meeting, ACS, New York, N. Y., Sept. 1957. (4) Friedman, S., Zahn, C., Kaufman,
11.L., Wender, I., BuMines Bull. 609 (1963). (5) Gerrard, W., Kilbarn, K. D., J. Chem. SOC.1956, p. 1536. (6) Langer, S. H,, Connell, S., Wender, I., J . Org. Chem. 23, 50 (1958). (7) Langer, S. H., Friedel, R. A., Wender, I., Sharkey, A. G., ANAL.CHEM.30, 1353 (1959). (8) Langer, S. H., Pantages, P., Wender, I. Chem. & Ind. (London),1958, p. 1664. (9) hukkainen, T., Vanden Heuvel, W. J. A., Hashti, E. 0. A., Homing, E. C., Biochim. Biophys. Acta 52, 599 (1961). (10) Sweeley, C. C., Bentley, R., Makita, M., Wells, W. W., J . Am. Chem. SOC.85, 2497 (1963). (11) Y l l s , W. W., Sweeley, C., Bentley, R., Gas Chromatography of Carbohydrates,’, chap. in “Biomedical Applications of Gas Chromatography,’’ pp. 169223, H. A. Szymanski, ed., Plenum Press, New York, 1964. (12) Zahn, C., Sharkey, A. G., Jr., Wender, I., BuMines Rept. Znv. 5976, 1962.
SIDNEYFRIEDMAN MARVIN L. KAUFMAN Pittsburgh Coal Research Center Bureau of Mines U. S. Dept. of the Interior Pittsburgh, Pa. 15213 WORKsupported in part by the Union Carbide Corp. Reference to a company or product name is made to facilitate understanding and does not imply endorsement by the U. S. Bureau of Mines.
Stability Studies on Ferric Thiocyanate Complex as Used for Determination of Micro Amounts of Chloride SIR: In 1952 a new colorimetric method for the determination of low concentrations of chloride was reported by Iwasaki, Utsumi, and Ozana (6). The method was reported to be based on the following reactions: 2C14C1-
+ Hg(SCN)2 FI HgClz + 2SCW+ Hg(SC?j)2 HgCld-’ + 2SCNSCN- + Fe+3 + Fe(SCN) +’
These authors stated that the color of the thiocyanate complex is fully developed after 10 minutes and is stable for several hours. They worked with chloride concentrations ranging from 0.1 to 20.0 pg. In 1957 Bergmann and Sanik ( 1 ) utilized the same method for analyzing trace amounts of chlorine in naphtha. Their working range was 0 to 50 pg. They, too, made their measurements after a 10-minute waiting period, stating that measurements should be made as promptly as possible because of the slow absorption of any chloride present in the air. Bergstresser (Z), in work reported in 1963, used essentially the same colorimetric procedure as Bergmann and Sanik (1) for the determination of
micro amounts of chloride in plutonium metal. He, too, made the spectrophotometric measurements as quickly as possible after a 10-minute waiting period. Recently, we made hundreds of spectrophotometric measurements of trace amounts of chloride using the ferric thiocyanate complex method. Our observations led to different conclusions concerning the stability of the complex and the factors governing this stability. These conclusions are based on the data of several special esperimental studies as well as on the evaluation of routine data. EXPERIMENTAL A N D RESULTS
Reagents. Ferric ammonium sulfate solution (0.25M in 9 N HN03). Mercuric thiocyanate solution (saturated in 95% ethanol). Standard chloride solution (0.2100 gram per liter of potassium chloride), Apparatus. A Beckman Model B spectrophotometer was used for all work except t h e spectral studies, which were made using a Cary Model 1 4 recording spectrophotometer. Procedure. Add 2 ml. of the ferric ammonium sulfate solution t o a 25-ml. volumetric vask containing approximately 18 ml. of a solution slightly basic t o phenolphthalein and 0 t o 50 pg.
of chloride. Then add 2 ml. of t h e saturated mercuric thiocyanate solution and mix the solution gently, dilute to volume, and mix again. Measure the absorbance after 10 minutes have elapsed from the time of mixing. Time-Absorbance Studies. Timeabsorbance studies were made in two ways. I n t h e first study, one-to-four absorbance measurements were made on five aliquots taken from each of six solutions, each containing a different known concentration of chloride. T h e aliquots were taken at regular time intervals. I n the second study, single absorbance measurements were made on each of two aliquots taken from a different set of chloride solutions. These solutions contained the same known concentrations of chloride, but the aliquots were taken a t widely separated time intervals. The results of the time-absorbance studies are shown in Table I. The results of the first study indicated only minimal variations in absorbance a t any chloride concentration level. The variations which did occur may be ascribed t o instrumental error. A duplicate experiment performed a t an earlier date exhibited essentially the same type of agreement among measurements. The results indicate color stability for as long as 75 minutes after mixing. The results of the second study indicated color stability of only 60 minutes VOL. 38, NO, 1, JANUARY 1966
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