Mild, Rapid, Hydroxyl Determination for Primary Alcohols JOSEPH A. FLORIA, IRVIN W. DOBRATZ,’ and JOHN H. McCLURE Research and Development Division, Organic Chemicals Department, Jackson laboratory, Wilmington, Del.
b A method for the mild, rapid, titrimetric determination of hydroxyl content of primary alcohols is described. The method involves a 10-minute esterification, a t room temperature, using 3-nitrophthalic anhydride and a novel basic catalyst, triethylamine. The use of an indicator simplifies the titration. This method is applicable to primary alcohols ranging in molecular weight from 32 to 20,000 and has good precision over this range. Secondary alcohols are only partially esterified and phenols and tertiary alcohols essentially do not react with the reagent. The only known interferences are those common to most hydroxyl determinations.
T
wet chemical methods for the determination of the hydroxyl content of primary alcohols normally employ the technique of esterification using ac;;l halides, anhj-drides. and acids, catalyzed by such reagents as pyridine! lierchloric acid, or boron trifluoride. -1general survey of the literature in this area, through 1959 has been summarized in articles bi. Nehlenbacher ( 6 ) , and Fritz and Schenk ( 3 ) . Kyriacou ( 5 ) suggested the use of zinccatalyzed acetylations of lower niolecular n-eight poly11ropylene glycols. Siggia, Hanna: and Culiiio (10) have reljorted raliid wterifications of primary and secondary alcohols in the presence of phenol using pyromellitic dianhydride. Robinson, Cundiff and 1Iarkunas ( 7 ) used pyridine to catalyze esterifications between 3,j-dinitrobenzoyl chloride and many primary> secondary, and tertiary alcohols, phenols. and polyhydroxy coni])ounds. Gutnikov aiid Schenk ( 4 ) acetylated, then hytfroxamated Ijriniary and secondary alcohols and supari for sliectrophotometric wtimations. Siggia and Hanna (8, g j , and I3udd ( I ) have desrribed kinetic differential acetylation-phthalation methods for the estimation of i)riiiiary aiitl secondary hydroxyl functions in alkylene oxide polyethers. Stetzler and Smullin (11) employed p-toliien~~sul~oni(~ acid to catalyze acrtylations of Carbonax and poly1
H E CLASSICAL
1)ecVessed
propylene oxide adducts to sorbitol. Bush, Kunzelsauer, and Merrill ( 2 ) demonstrated the use of phosgene followed by an argentimetric titration for the determination of lower molecular weight polyethylene glycols. In general the chemical methods of analysis exhibit limitations when apof higher molecular weight liriniary, O , w’-polyether glycols. During these studies, esterifications conducted with acetyl chloride, catalyzed by pyridine, under reflux, were too drastic, resulting in fragmentation of the polyether linkages, while the acetic anhydride-pyridine esterifications a t a slightly elevated temperature (35’ C.) proved too lengthy for routine analysis, requiring 22 hours for complete reaction. In order to circumvent these limitations, a study of other esterification reagents and catalysts was undertaken. Veraguth and Diehl (12) had used 3-nitrophthalic anhydride as an esterification reagent applicable to the lower molecular weight Iiolyethylene glj-cols, namely the monoethers of ethylene and diethylene1 glycol. Their procedure involved heating a toluene esterification mix below 110’ C. I t was thought that the addition of pyridine, a proton acceptor, to the reaction mix would possibly effect esterifications a t lower temperatures. I-nder these conditions, with ethylene g1 60 to 7OyOconversion obtained at room temperature within 30 minutes. Based on this encouragement, an investigation of more proteophilic bases was undertaken with the final selection of triethylamine. The presently developed procedure is very rapid, requiring 30 minutes per analysis. Esterification conditions are mild and do not cause rupture of the carbon-osygen bonds. The method is versatile and applicable to primary alcohols ranging in molecular w i g h t between 32 and 20,000. EXPERIMENTAL
.I-, .Y- D I hi E TH T LF o R 11Reagents. A M I D E (I?AIF). Add 100 grams of Liiide 5-4 llolecular Sieves to each 4 liters of IIAIF, mix thoroughly, and allow to htand ovcxrnight. 0.2.11
3 - ~ I ? . R O P H T H . . \ L I C ;\NHTI)RII)I.;.
Dissolve 38.0
*
0.5 grams of 3-nitro-
E.
1. du font de Nemours and Co.,
phthalic anhydride (Eaytman Iiodak Khite Label) in about 500 nil. of dry IIMF contained in a l-liter3 lon-actinic glass: volunietric flask. Fill to volume w t h dry D l I F and niix thoroughly. 0.1.v T I . : T R . 4 B U T Y L 4 J I . \ I O S I ~ ~ l HYIIROXIDI.:. .ldd 190 nil. of methanol to a 1-liter volumetric flask. Add 100 ml. of 1.0.U methanolic tctrabutylamnioniuin hydroxide reagent (Southwestern .%nalytical Chemicals; €’. 0. 13ox 485, dustin, Texas, Catalog S o . 304). Fill to volume with benzene and mix thoroughly. Standardize thiq reagent against I‘. S. Sational I3ureau of Standards Grade benzoic acid (0.55 gram) dissolved in dry DLIF, uiing thymolphthalein indicator. The end point is manifest by a permanent blue color. 1% THTMOLPHTHALF Dissolve 1.00 gram of thpiolphthalbin in 99 1 grams of dry D N F . TRIETHTLARIISI:. Eastman Kodak JThite Label. During the study. on[’ lot of reagent out of ten wah encountered which did not behave iirolierly in the esterification, producing abnorma!ly low blank titers. S o apiiarent difference was detected between acceljtable and inferior materials by X N R or IR analyses. Sear-IR investigations indicated traces of primary and or secondary amines. I t is recommended that a standard alcohol sample be analyzed whenever a nen- lot of amine is illaced in service. Procedure. Determine the ai)propriat8e amount of sample ( 2 milliequivalents) to be used in thc analj..i,from the following relat,ionsliilj:
*
grams sample
=
2.0__ __ expected hydroxyl (iiieq.; gm.) then weigh (+0.001 gram) the proper amount of sample into a 250-ml. Erlenmeyer fl blank a t this point by adding ell subsequent reagent:: to another Erlenmeyer flask. Pipet 50 nil. of dry 1)NF into the flask. Warm if necewuy to not more than 70’ C.to effecat hami)le solution. Cool the flask arid it. content:: to room temperature. Pipet 5.0 nil. of triethylaiiiine and swirl to mis. Pillet 25.0 nil. of 0.2.1/ 3-nitrol)hthalic. anhydride in dry DAIF. Swirl to mix. stolil)er, and nllovi to stand for 10 1 minutes, a t room trmijcratuw. Iiiimediately 1)ipet 1 ml. of dihtillrd m t t v into the fla& 11ix and allon. to .stailti a inininiuni of 10 niinutw at room teinliernture, agitating intcmiittt~ntly. . i d t i
*
VOL. 36, NO. 11, OCTOBER 1964
2053
RESULTS
5
0
IO
15
20
ML. TRIETHYLAMINE Figure 1 , Effect of triethylamine on the degree of esterification of n-octanol
10 to 15 drops of 1% thymolphthalein indicator solution and titrate with standard, 0.1N tetrabutylammonium hydroxide to the thymolphthalein end point (first appearance of a yellow-free green color). Determine any free acidic or basic materials using a separate sample. The milliequivalents per gram of hydroxyl is calculated from the difference between the blank and sample titers with suitable corrections for the presence of free acidity or alkalinity.
Table
I.
The study of amine catalysts was limited exclusively to tertiary amines, since both primary and secondary amines react with the 3-nitrophthalic anhydride. Tri-n-propylamine, triisobutylamine, and triethylamine were evaluated during the course of this study. Of these three, only triethylamine provided the necessary proteophilic activity for complete esterifications a t room temperature. The amount of triethylamine necessary to produce complete esterification, using the procedure outlined above, is shown in Figure 1. From the data illustrated, a volume of 5 ml. (36 milliequivalents) of triethylamine was selected as a workable amount of reagent. During the course of a statistical correlation study between the above 3-nitrophthalic anhydride-triethylamine procedure and the acetic anhydride-pyridine method (35" C.) for hydroxyl analysis, an indication of a sample size-hydroxyl value dependence appeared. As the equivalent ratio of reagent to sample was varied from 5 to 1 to 20 to 1, the hydroxyl values varied from 0.095 to 0.160
Precision and Accuracy of the 3-Nitrophthalic Anhydride Method
3-Sitrophthalic anhydride Acetic anhydride method method, Polyethylene Polyethylene polyethylene Materials glycol 400 glycol 20,000 glycol 20,000 Theoretical hydroxyl value, meq./gm. 4.98" 0 . lOOb 0. l O O b Number of determinations 20 20 10 Average hydroxyl value found, meq./gm. 4.99 0.101 0.105 Standard deviation, meq./gm. 0.013 0,001 0,001 a Hydroxyl content calculated from molecular weight (401.7) determined ebullioscopically . b Theoretically assumed hydroxyl content based on a molecular weight of 20,000.
Table II.
Alcoholsa Methanol Ethanol, absolute Isopropanol n-Butanol sec-Butanol &Butanol n-Pentanol t-Pentanol n,-Ortanol
Determination of Hydroxyl Content of Alcohols
Source Math., Col., and Bell U. S. Indust. Chem. Math., Col., and Bell Eastman Kodak Math., Col., and Bell Math., Col., and Bell Math., Col., and Bell Math., Col., and Bell Eastman Kodak Eastman Kodak Du Pont Mallinckrodt DU Pont Carbide Carbide Carbide
Meq./gm. Hydroxyl Theoretical Found 31.2 30.2 21.7 21.2 16.6 5.35 13.5 12.8 13.5 3.74 13.5 Xi1 11.3 11.2 11.3 0.023 7.68 7.52 3.69 3.58 3.26 10.0 0.317 10.6 32.2 31.6 5.0lb 4.99 3.33b 3.28 0,333 0.335 0.100 0.101 0.702 1.65b 32.6 26.9 20. I * 20.1
%
Recovery 96.8 97.7 32.2 94.8 27.7 Nil 99.1 0.2 97.9 97.0 32 6 2 99 98 1 99 6 98 5 100 6 101.0 42.5 82.5 100.0
n-Octadecanol Cyclohexanol Phenol Ethylene glycol Polyethylene glycol 400 Polyethylene glycol 600 Polyethylene glycol 6,000 Polyethylene glycol 20,000 Dow Polypropylene glycol Dow Mallinckrodt Glycerol Trimethylolpropane Cellanese a All alcohols were used as received. b Meq./gm. hydroxyl calculated from molecular weigln t determined ebullioscopically
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ANALYTICAL CHEMISTRY
Figure 2. Effect of sample size on hydroxyl value of polyethylene glycol
20,000 meq./gram. This effect is shown in Figure 2. Further studies revealed that in order to obtain accurate hydroxyl analyses, a 5- to 1-equivalent reagent to sample ratio was required. This implies that a preliminary analysis may be necessary to establish the approximate hydroxyl content. A net titer of 20 f 2 ml. provided satisfactory precision in the measurement of the volume of tetrabutylammonium hydroxide. Sample sizes were then chosen to maintain the reagent to sample ratio and the titer specified. The 10-minute reaction time was selected after studying esterification time requirements for various alcohols, namely, n-octanol, and commercially available polyethylene glycols of 400, 600, and 20,000 molecular weights, respectively. I n each case the time required for most precise and accurate hydroxyl analyses was 10 minutes. The volume of water necessary to hydrolyze the unreacted anhydride could be varied between 1 and 14 ml. without affecting results. The use of volumes greater than 14 ml. caused a shift in the end-point potential. One milliliter of water provided a satisfactory excess for complete anhydride hydrolysis and did not influence either potentiometric (Dow-Precision Titrator) or visual titrations. A study of various indicators in the reaction mass being titrated potentiometrically, using a Dow-Precision Titrator, showed that thymolphthalein was the only indicator of those tested which exhibited a color change a t the endpoint potential. A study of the standard deviation of the 3-nitrophthalic anhydride method was made on samples of both polyethylene glycol 400 and polyethylene glycol 20,000, to define the precision of the method. The accuracy of the method was found by determining the milliequivalents/gram of hydroxyl on polyethylene glycol 400, the molecular weight of which was independently established by ebullioscopic means. I t was further
confirmed at higher molecular weights by comparing the ~ ~ ~ a l uobtained es using the acetic anhydride-pyridine and 3-nitrophthalic anhydride-triethylamine methods 011 a 20,000 molecular weight sample of polyethylene glycol, where no absolute knowledge of its hydroxyl content was available. A summary of the precision and accuracy studies are shown in Table I. h close correlation was attained between the two independent methods of analysis on polyethylene glycol 20,000, while the 3-nitrophthalic anhydride method gave good agreement in the polyethylene glycol 400 case. The standard deviations in all cases fell within approximately 11%of the average milliequivalents/gram of hydroxyl in the two materials under consideration. Table I1 lists many of the alcohols studied and demonstrates the applicability of the method. From the data it is readily seen that the method is applicable only to primary alcohols. I n the case of the polypropylene glycol, some serondary alcohol groups are present, the assumption being that synthesis with propylene oxide can produce either primary or secondary terminal alcohols. Similarly, glycerol, containing a secondary alcohol group, is not completely esterified. INTERFERENCES
Primary and secondary aliphatic and aromatic amines will react with the reagent and will interfere with the determination.
Table Ill.
Time and Temperature Effects on Meq./gm. Hydroxyl for Secondary Alcohols
Alcohols Isopropanol
.set-Butanol
Glycerol Glycerol Glycerol Glycerol
T(pp., C. 25 25
0 25 40 60
10 min. 5.35 3.74 24.4 26.9 27.8 30.0
Secondary alcohols do not react quantitatively with the reagent. This is best shown in the data obtained from extended time and increased temperature studies performed on this class of alcohols. Results of this study are shown in Table 111. While both extending the reaction time and increasing the reaction temperature increase the degree of esterification, much more rigorous esterification conditions would be required, in order to attain quantitative results in a reasonably short time. Tertiary alcohols do not esterify with the reagent. The presence of water interferes with the determination by hydrolyzing the anhydride. ACKNOWLEDGMENTS
The authors wish to express their appreciation to J. R. Martin for his interest and helpful suggestions, and also to R. bl. Baillie, Jr., who performed all of the experiments connected with this development.
Meq./gm. Hydroxyl 30 min. 60 min. 120 min. 10.7 13.8 l;, . 5 7.66 10.5 12.2 26.9 29.3 ... 29.6 30.3 30.8 30.6 ... .. 30.2 .,. , , ,
Theory 16.6 13.5 32,6 32 6 32 6 32 6
LITERATURE CITED
(1) Budd, 11. S., AXAL. CHEY.34, 1343 i1962).
Bush, D. G., Iiunzelsauer, L. J., LIerrill, S.H., Zbid., 35, 1251 (1963). ( 3 ) Fritz, J . S.,Schenk. G. H.. Zbid.. 31, 1808 i 19j9). (4)Gutnikov, G., Schenk, G. H., Z b i d . , 34, 1316 (1962). ( 5 ) Kyriacou, U., Ibid., 32, 291 (1960). (6) Nehlenbacher, V. C., "Organic Analysis," Vol. I, - pp. 1-38, Interscience, Sew York, 1903. (7) Robinson, W. T., Cundiff, R. H., Uarkunas, P. C., ANAL. CHEY. 33, 1030 (1961). (8) Siggia, S., Hanna, J. G., I b i d . , 33, 896 (1961). (9) Siggia, S , Hanna, J. G., J . Polymer Sci. 56. 5 6 , 297 11962). (1962). (10) Sigiia, Siggia, S.,~ S., Hanna, J. G., Culmo, R., ANAL.CHEM.33, 900 (1961). (11) Stetzler, K. S., Smullin, C. F., Ibid., 34, 194 (1962). ( 1 2 ) Veraguth, A. J., Diehl, H., J . Am. Chem. SOC.62, 233 (1940). (2j
RECEIVEDfor review April 29, 1964. Accepted August 3, 1064. Division of A4nalyticalChemistry, Fisher Award Symosium honoring John llitchell, Jr., 147th !leering, ACS, Philadelphia, Pa., April 1964.
A Low-Level Carbon-1 4 Counting Technique L. T. FREELAND Plastics Department, Mcrnufacturing Division, E.
b Liquid scintillation spectrometry has proved very useful in the dating of carbon- 14 containing artifacts. However, most carbon- 14 dating methods involve a tedious and usually low yield preparation of a suitable solvent for liquid scintillation spectrometry. The possibility of isotope effects is present in some of these procedures. This paper describes a tmechnique which circumvents the before mentioned limitations. The method requires the combustion of the scimple to COz, absorption of the CO:!in sodium hydroxide solution, followed by reaction with phenylmagnesiuni bromide to form benzoic acid. The benzoic acidC I 4 is esterified to methyl benzoate. This methyl benzoate is the solvent used in the assay of the sample by liquid scintillation spectrometry.
I . du Pont de Nernours & Co., Wilrningfon, Del.
SCINTILLATION spectrometry been used previously to determine both contemporary and lower concentrations of carbon-14 ( I , 2 , 8 ) . The syntheses of the solvent compounds for liquid scintillation counting have been time consuming, involved, and apt to produce chemical yields of usually less than 60% (3, 5 , If). This paper describes a method of stabilizing the liquid scintillation spectrometer and a simple method for synthesis of the solvent compound in high chemical yields. The stabilization of the liquid scintillation spectrometer is necessary because o the long counting times (24 to 72 hours) requ'red by the low concentrations of carbon-14. The method depends upon the complete combustion of the sample to CO, and the reaction of the resulting COz with phenyl-
c"h:s
magnesium bromide to yield benzoic acid which is esterified to methyl benzoate. The methyl benzoate is the radioactive sample as well as the solvent for the phosphor for liquid scintillation spectrometry. The overall chemical yield from original sample to purified methyl benzoate is 85 to 87%. EXPERIMENTAL
Liquid Scintillation Spectrometer. Samples were counted in a Tri-Carb Liquid Scintillation Spectrometer, Model 314-DC (Packard Instrument Co., La Grange, Ill.). T h e freezer containing samples, photomultiplier tubes, and preamplifiers is maintained at 0" C. T h e instrument is operated on an isolated electrical circuit equipped with a constant voltage regulator. The VOL. 3 6 , NO. 1 1 , OCTOBER 1 9 6 4
2055
