Chromatographic Determination of Codeine in Opium and Other Complex Mixtures GEORGE C. MCELHENY, GEORGE DELAMATER,and ROBERT D. RANDS M a l l i n c k r o d t Chemical Works, St. Louis, M o .
papaverine>narcotine, morphine>narcotine, morphine>codeinr. Their attempts to work out a general method for the separation of the principal opium alkaloids, however, were not successful. More recently Girard ( 2 ) described a micromethod for the separation of morphine and hydroxydimorphine on alumina. In 1949 Stolman and Stewart ( 9 , 10) developed a microchromatographic method for the determination of morphine, codeine, and heroin in viscera and body fluids using Florisil as the adsorbent and methanol as the eluant. Sapara (8) has described the use of alumina for the separation of codeine, morphine, narcotine, and thebaine. In 1951 Baizer ( I ) described a method for partially separating dihydrocodeine from dihydroisocodeine on alumina using ethylene dichloride ( lj2-dich1oroethane) as the eluant. Very recently Iilee and Kirch (4)have applied Stolman and Stewart's chromaS tographic method for determining morphine in body fluids to the determination of morphine in opium. Few of the above methods allow wparations that are complete enough for analytical work and in most cases the alkaloids were not recovered quantitatively from the adsorbents.
The work described was undertaken to provide a convenient and accurate method for the determination of codeine in opium and other complex mixtures. Opium is extracted with a saturated solution of sodium acetate. The nonphenolic alkaloids are isolated as a benzene solution and are separated on a column of alumina with the aid of special developing solutions. The advantages of this method over previous ones are: The opium residues are thoroughly extracted, a correction factor is not required, since there is n o loss of codeine, and the codeine is separated conipletely from neopine, thehaine, and other opium alltaloids.
T
HI: pain-relieving and habit-forming properties of opium have been known for centuries. Because the physiological activity of opium itself is due principally to morphine (Figure 1). most of the chemical work concerned with the analysis of opium has dealt with this single alkaloid. h s a result, a number of procedures for assaying morphine in opium are now available. The lesser alkaloid* of opium were originally of little medical importance, and the study of their occurrence in opium lagged fai behind that of morphine. I n this century, however. there ha. come the realization that codeine may be substituted for morphine in many preparations, such as antitussives or scdativeq, where its milder Fide effects and lower addiction liability make it the drug of choice. As a result there has been increased intcreit in the extraction of codeine from opium. The absence of accurat(i :tnalytical methods for the determination of the codeine content of opium and other mixtures prompted the work described. Thv resulting chromatographic method of analysis proved to be geiiwally applicable not only to opium but also to internicdiatr+. auch as occur in the processing of raw opium, and to cornplo\ pharmaceutical preparations containing codeine. The chromatographic method has been applied in these lahor:~tories t o the separation and determination of other alhaloids 01 opium. By the method dexribed thebaine, cryptopine, neopine. papaverine, and narcotine are eluted from the column hefoi(s codeine and are separated completely from it but not from on(' another. The separation and determination of thebaine, papaverine, and narcotine will he described in a future paper. -1number of methods for the analysis of codeine have bee11 published. I n general, these methods have depended upon separation of the codeine from a mixture containing many othei alkaloids, some of similar structure, by means of selective extraction with immiscible solvents or by precipitation of qparingl) soluble salts of codeine. These methods are inaccurate. perhapr ciq a consequence of varying amounts of impurities which cauw variations in the completeness of extractions and precipitations. -1s the cihromatographic technique has been used effectively foi heparating many complex mixtures, it appeared to offer a possible ioute to better methods of analysis for the opium alkaloids Partial separations of some opium alkaloids have been achieved by previous investigators. As early as 1937, Kondo ( 6 ) attempted to separate artificially prepared mixtures of niorphinr). codeine, thebaine, and narcotine on alumina using ether as a11 eluant. He met with some success in partially separating thrbine from morphine, and rodeine and narcotine from thebaine. Levi and Custelli (6, t ) deposited synthetic mixtures of the. alkaloids on calcium carbonate and, using 90% ethyl alcohol as the eluant, recorded the following relative adsorption affinities:
,CH3
,C"3
HO MORPHINE
CODEINE
NEOPINE
THEBAINE
Figure 1.
Opium Alkaloids
The chromatographic method described below has been used on a routine basis for the precise analysis of codeine in such divers? samples as opium, factory process liquors, and tablet mixtures. A striking example of the specificity of this method is the complete separation, in a single step, of codeine and neopine, which differ solely in the position of a single carbon-carbon double bond (Figure 1). These two compounds have previously been separahle only by laborious and repeated fractional crystallization ( 3 ) . APPARATUS
Waring Blendor, optional. Automatic Fraction Collector, optional. Chromatographic Tube. The chromatographic tube is a 1.8em. (inside diameter) borosilicate glass tube about 50 cm. long with a stopcock a t the bottom. To the upper end is sealed a 500-ml. round-bottomed flask which serves as a reservoir. At
819
820
ANALYTICAL CHEMISTRY
the lower end a plug of rotton or glass wool acts as a support for the adsorbent. Continuous Codeine Extractor. Figure 2 shows the assembled extractor. The solution to be extracted is contained in the extraction column. Benzene is distilled from the boiler, the vapors rise to the condenser, are liquefied, and flow down the tube to the space below the sintered-glass disk a t the bottom of the extraction column. The benzene asses through the disk and emerges as droplets ranging in size Eom 1 t o 3 mm. in diameter. The droplets rise through the solution and form a separate layer a t the top of the column. The benzene flows through the overflow tube into a trap and then is returned to the boiler. After several hours, all of the codeine and other benzene-soluble substances are present as a benzene solution in the boiler.
n
S T A I N L E S STEEL NECK 1-1/21ao.x **LONG
R U M R TUBING CONNECTORS
i P
STEAM
\ 1/11
S
T
E
A
Y IN
STAINLESS STEEL BOILER 4-3muoa X 6-3/4' HIM
mrn-
TO ORAIH
PYREX EXTRA-COAR$E 8IWTCRED M8C 8- WOIA
Figure 2.
Codeine Extractor
Syringe Pipet. The pipet is prepared from 10-mni. outside diameter glass tubing by drawing it down to a 1- to 2-mm. capillary 10 cm. long on one end and a short (2 cm.) thickened capillary on the other which is inserted into a Yo. 0, one-hole rubber stopper. A 5-ml. hypodermic syringe is inserted in the other end of the stopper. SPECIAL REAGENTS
Aluminum Oxide, Merck reagent, suitable for chromatographic adsorption. Sulfuric Acid, 0.0500N. Chromatographic Developing Solutions. 801ution 1 2
Isopropyl Alcohol Vol., % ml. (v./v.) 6 1.5 20 5
Chloroform Vol.. nil. (v.?v., 40 10 40 10
Benzene Vol., 57, 1111.
(v./\-.)
354 340
88,s 85
\-olrime ITsed, Afl. 370 350
Acidified Sodium Acetate Solution, prepared by adding 1 volume of glacial acetic acid to 50 volumes of a saturated aqueous solution of sodium acetate.
PROCEDURE
Extraction of Codeine from Opium. Disintegrate 50 grams of opium in a Waring Blendor containing.200 ml. of water. (If a Waring Blendor is not available, the opium can be cut into small pieces, soaked in water for several hours, and then triturated in a mortar.) Transfer the resulting slurry to a 1-liter glass bottle. Rinse the blender three times with a total of 550 ml. of saturated sodium acetate solution and add the rinsings to the original extract together with 100 grams of sodium acetate trihydrate and 15 ml. of glacial acetic acid. The pH of the resulting slurry should be between 6.0 and 7.0 as determined with bromothymol blue paper. If the pH is too high add more glacial acetic acid. Heat the bottle in a water bath to about 40" C. for from 4 to 5 hours with occasional agitation. Filter the resulting mixture through a 24-cm. rapid filter paper into a 2-liter Erlenmeyer flask by inverting the bottle over the funnel with its mouth below the top of the paper and allowing the filtration to proceed automatically overnight. Rinse the bottle with enough acidified sodium acetate solution to fill the aper filter. When filtration is complete, transfer the insolubre residue and filter paper t o a 1-liter Erlenmeyer flask and reslurry it with 400 ml. of acidified sodium acetate solution. Heat the slurry on a steam bath for 1 hour with occasional stirring. Filter the mixture as before and wash the residue with enough acidified sodium acetate solution to bring the total volume of extract up to 1750 ml. Boil 600 ml. of benzene in the boiler of the codeine extractor until the solvent fills the space below the sintered-glass disk in the extraction column. After pouring the opium extract into the long vertical column, make it alkaline to phenolphthalein test paper by the addition of sodium hydroxide solution and extract it for 6 hours. Eva orate the resulting benzene extract in the boiler to about 100 m f a n d transfer it to a 250-ml. separatory funnel, rinsing the boiler with several small portions of benzene to ensure that the codeine is transferred quantitatively. Extract the benzene solution with a mixture of 10 ml. of dilute sulfuric acid (10%) and 30 ml. of water. Filter the aqueous layer into a 200-ml. volumetric flask. Extract the benzene three more times with 30-ml. portions of water containing about 1 ml. of dilute sulfuric acid, and add the extracts to the volumetric flask. Rinse the filter paper carefully m t h each succec sive extract, and finally with several milliliters of water. Dilute the combined extracts to volume with water. Estimate the total alkaloids present. in the acid extract by making an aliquot of the solution alkaline wlth sodium hydroxide, extracting it with benzene, eva orating the benzene to dryness, dissolving the residue in alco 01, and titrating it with standard acid. Each milliliter of 0.1.4' acid consumed is equivalent to 29.94 mg. of total alkaloids in the.aliquot expressed as codeine. For the chromatographic analysls, use an aliquot which contains from 400 to 500 mg. of alkaloid expressed as codeine. Pipet the necessary volume of aqueous solution into a suitable separatory funnel and cover it with an approxhately equal volume of benzene. Make the solution strongly alkaline to phenolphthalein by adding sodium hydroxide solution and shaking the solution for about 1 minute. Separate the aqueous layer and reserve it for further extraction. Draw about 25 ml. of. the benzene layer into a 100-ml. beaker and stir with 1 gram of anhydrous potassium carbonate until any trace of moisture has disappeared. Then decant the benzene through a rapid filter paper into a 250-ml. beaker. Use the same potasslum carbonate to dry the remainder of the benzene layer, combining the benzene portions and evaporating them to dryness. Dissolve the potassium carbonate in the a ueous layer and transfer it to a separatory funnel and repeat the L o v e benzene extraction and drying procedure three times, evaporating all four benzene extracts in the same beaker. Dissolve the residue completely in 10 ml. of fresh benzene and transfer it to the chromatographlc column. Extraction of Codeine from Liquid Samples. Analyze aqueous solutions containing codeine by extractlng an aliquot containing about 500 mg. of total alkaloids with benzene as described in the last paragraph of the preceding section. (This procedure has been applied with success to impure samples taken from factory processing of opium.) Extraction of Codeine from Tablet Mixtures. Grind the tablets to a fine powder and wash a 50.00-gram sample into the continuous codeine extractor with water. Make the solution strongly alkaline to phenolphthalein by the addition of sodium hydroxide and extract it for 6 hours with benzene. Evaporate the benzene solution to about 100 ml. and extract it with dilute sulfuric acid as previously described. Extract the combined acid extracts with two 50-ml. portions of chloroform to remove caffeine and acetophenetidine (phenacetin). Back-wash the chloroform extracts with two 10-ml. portions of acidified water.
K
821
V O L U M E 26, NO. 5, M A Y 1 9 5 4 Combine the aqueous extracts and dilute them to 200 ml. in a volumetric flask. Treat this solution as described in the last paragraph of the section on extraction of codeine from opium. Chromatographic Separation of Codeine from Other Nonphenolic Alkaloids. Add a slurry of 125 grams of aluminum oxide in 130 ml. of reagent grade benzene to the chromatographic column using a funnel. Wash t,he residual alumina in the beaker and funnel into the column with an additional 15 ml. of benzene. Open the stopcock and tap the column while rotating it by hand in order to eliminate any bubbles trapped in the slurry and settle the alumina uniformly in the column. Drain the excess benzene from the column, closing the stopcock just before the level of the benzene reaches the surface of the alumina. The column is ready now for t'he deposition of the sample. Take care a t all times to prevent the top of the alumina column from drying and cracking. Transfer the solution of alkaloids in benzene, prepared as described above, to the column with a pipet, preferably the special syringe pipet described. Open the stopcock a t the bottom of the column until the sample has drained almost to the surface of the alumina. Rinse the beaker twice with 5-ml. portions of benzene using them to rinse down the sides of the column. iifter each portion has been added to the column, open the stopcock until the liquid has drained to the surface of the alumina. Care should be taken during all transfers to avoid disturbing the surface of the alumina. Calculate the holdup volume, which is of value in determining the point a t which a fresh solvent emerges from the column, by subtracting the volume of benzene drained from the column from the sum of the volumes used in preparing the column and depositing the sample. (The holdup volume varies from 95 to 105 nil. for the column described above.) Add chromatographic developing solut'ion 1 to the column, open the stopcock, and discard the first 340 ml. of effluent solution. Collect equal volume fractions of approximately 20 ml. in a graduated cylinder and transfer them to individual 100-ml. beakers, or use an automatic fraction collector which greatly facilitates the anal JVhen less than 15 ml. of solution 1 remains above the s ce of the alumina add developing solution 2. Collect fractions until all of the solution has run into the column. Evaporate each fraction to dryness on a steam bath and dissolve the residue in 10 ml. of methanol with warming. Add distilled water (50 ml.), previously adjusted to pH 4.8 with 0.1S sulfuric acid, and titrate the solution with 0.05,Vsulfuric acid to 3 pH of 4.8 using a pH meter. Plot the milliliters of acid required for the titration of each fraction as a function of the fraction number. Calculate the weight of anhydrous codeine in the sample by inserting in the following equation the sum of the volume? of standard acid required for the titration of the fractions comprising the codeine peak (see discussion). Keight of codeine in grams = ml. of acid X normality X X 299.4, where 299.4 is the equivalent weight of codeine. From the calculated weight of codeine, the weight of the original sample and the size of the aliquot, compute the percentage of codeine in the original sample. Time can be saved by carrying out several analyses concurrently. When this is done, about eight working hours are required to complete one analysis, the elapsed time being 3 days.
in acidified sodium acetate solution, whereas many of the colored impurities and weak alkaloid bases of opium, such as narcotine and papaverine, are not. This solution was chosen in preference to mineral acids, in which all of the above substances are soluble, in order to obtitin a better separation. Rate of Flow. The gravity flow of the developing solution through the alumina in the column described is such that the separation of alkaloids is satisfactory. This rate of flow has been found to fall within the limits of 3 to 5 ml. per minute. Column Dimensions. The column dimensions suggested for the analysis of codeine give satisfactory results but are not critical. Changes in length and diameter niay be made within reasonable limits, but the ratio of length to diameter should not be less than 15 to 1. An increase in column length result8 in increased resolution and separation while an increase in diameter permits greater quantities of material to be handled. When changes in dimension are made, the volumes of the solvents employed should be changed in proportion to the eight of adsorbent used. Vnder these conditions the peak effluent volumes are also proportional to the weight of adsorbent. Solvent System. Preliminary experiments sho\s ed that pule chloroform eluted the alkaloids as rather sharp peaks but effected little separation. On the other hand, benzene plus a little alcohol gave a fairly good separation of codeine fioni the other alkaloids but the peaks spread out to such an extent that the separation of neopine from codeine v a s not complete. The addition of 10% of chloroform to the alcohol-benzene solution has the effect of narrowing the neopine peak so that codeine is completely separated. The change from 1.5 to 5°C alcohol solution is made so that the codeine xi11 be eluted rapidly in a few fractions of high concentration as sooii nu the othei alkaloids have passed out of the column.
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~
=Or
I
i ''Or
4
1
DISCUSS103
Tablet Mixtures. Tablets containing aspirin, acetophenetidine. caffeine, and codeine can be readily analyzed for codeine. The aspirin remains in the alkaline solution in the codeine estractor. Any caffeine or acetophenetidine which is not removed by the chloroform extraction and any phenetidine which results from hydrolysis of acetophenetidine are eluted from the column considerably sooner than the codeine. Thus, in the final titration codeine is the only base present, all others having been eliminated. Size of Sample. The maximum weight of alkaloids which niay be chromatographed satisfactorily on 125 grams of alumina ia about 500 mg. If more than 500 nig. of material is deposited, the codeine is partially eluted uith the 1.57' solution of isopropyl alcohol, and a hump or shoulder is produced on the codeine peak. With samples of unknomn composition this hump ma>- be mistaken for another alkaloid. In addition, with very large samples -ome of the peaks may overlap. AcidSed Sodium Acetate Solution. Codeine is readily soluble
IRACTIO*
MUYILR
Figure 3. Chromatograph Showing Separation of a Piire Mixture of 290 Mg. of Codeine and 129 3lg. of Neopine 20.5-W. fractions
Peak EWuent Volume. The various compounds eluted from the column appear in the graph as a series of peaks. The peak effluent is that volume of effluent collected while a given compound moves from the top of the column to the bottom and is measured at the point a t which the greatest Concentration of the compound is eluted. K i t h the procedure described here, the peak effluent volume of the combined neopine-thebaine fraction varies from 340 to 360 ml and that of codeine varies from 470 to 500 ml. End Point of Titration. It is suggested in the recommended
822
ANALYTICAL CHEMISTRY
procedure that a pH meter be used to determine the end point of the titration. Although the end point may be determined visually using methyl red, the latter is more susceptihlr to subjective error, especially when the quantity of arid required is small. Graphing the Results. I n the analysis of relatively pure samples, the codeine peak is sharply defined and the fractions immediately preceding and following it require a negligible quantity of acid for titration (see Figure 3). Under less favorable circumstances, it may be necessary to extrapolate the beginning and the end of the peak to eliminate the effect of impurities which are eluted near the codeine peak. The rurve obtained from the elution of a pure sample of codeine ail1 serve as a model for proper extrapolation. An example of an analysis where extrapolation is necessary is shown in Figure 4.
tlraetir than that with slightly acid sodium acetate, and from ihese results one concludes that the original sodium acetate extraction was nearly complete. The transfer of codeine from the original aqueous solution to henzene in the continuous extractor was investigated by extracting an accurately measured quantity of pure codeine. The benzene extract was then evaporated to dryness and the codeine residue determined by titration. The results of two such esperiments shown in Table I indicate that the recovery is quantitative.
Table 111.
Over-all Precision for .issay of Codeine in Opium ___ __ Codeine, "c
Sample
Issay
SO.
1
1
4 01 3.87 1 18
'7
3
nt
1
A
Tahle IV. Saiiiple
Aqsay
Precision in Chromatographic Step Codeine, 70 Assay
Origin of Saiiiple Opium Opium Opium Factory process liquor Factory process liquor Opium Opium
NO.
1 2 3 4 .j
6 7
Average 4.00 3.86 1.18
2 3.99 3.84 1.19
Assay 2 4.00 3.72 3 87 19.12 17.57 3.88 1.06
1
4.02 3.71 3.80 19.14 17.49 3.87 1.07
Average 4 01 3.72 3.84 19.13 17.53 3.88 1.06
___~
FRAOTION
The separation and recovery of alkaloids by means of the chromatographic column were investigated by analyzing known mixtures. The results of a number of such emeriments are shown in Table 11. These assays of mixtures of pure alkaloids indicate that essentially all of the codeine is eluted from the a1umin.a and that merhanical losses are negligible. These results indicate that the chromatographic method gives results which deviate less than 2% from the true value. precision. The over-all precision for the assay of opium is shown in Table 111.
NUWLR
Figure 4. Chromatograph from an Assay of a Very Impure Codeine Mother Liquor from the Factory 18.8-Ml. fractions
Accuracy. A study of the over-all accuracy has been made hy investigating the accuracy of the individual steps. The extraction of opium with sodium acetate solution was studied in the following experiment,. The residue remaining from the extraction of 50 grams of opium as described above was triturated once with water and four more times with dilute sulfuric acid adjusted to pH 2, the mixture being filtered after each extraction. From the water extract,, 19 mg. (0.038%) of very impure codeine was recovered. From the four acid extracts, less than 6 mg. (0.012%) was obtained. The original sodium acet'ate extract from the assay contained 1.93 grams (3.86%) of codeine. Thus the sodium acetate solution contained 99% of the codeine. The extraction with dilute sulfuric acid (pH 2) is much more ___Table I.
Percentage Recovery of Pure Codeine from the Continuous Extractor Extraction ~ i Hours 3 3
Run NO.
I 2
Table 11.
Run So. 1 1
3 1 3
~ Codeine ~ Alkaloid, , 11g. Added Recovered 952 9 49 954 954
R
~
~
Seopine Alkaloid, Mg. Recovered 302 61 62 none ... none ... none ...
...
...
...
Added 467 486 814 814 814
Rlg.
Recovered 465 484 809 812 810
.. %
I30
m
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'1 5
1.20
e o'2m
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m
'
loo
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8 0 oao = d
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~
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090
~
,
~
~
~
,
99.7 100.0 I5
16
Recovery, 70 99.6 99.6 99.4 99.8 99.5
18
20
22
24
26
28
30
32
34
36
FRACTION NUMBER
Figure 5 .
Codeine Alkaloid, Recovery, % 99.2 102.0
0
%
Percentage Recovery of Codeine and Neopine Alkaloids from Alumina
Added 304
-
Use of Ultraviolet Absorbance Ratios as a Criterion of Purity of Chromatographic Fractions 19.4-MI. fractions Absorbance ratios 1 Codeine 0.897 i. 0.005 2: Thebaink, 0.859 i 0.005 3. Neopine, 1.29 + 0.05 4. Papaverine, 1.34 zk 0.05 5. Fractions from column
V O L U M E 26, NO. 5, M A Y 1 9 5 4 The precision of the chromatographic separation alone was investigated by performing duplicate analyses on aliquots of impure solutions of codeine salts. The results of these analyses are shown in Table IV. Purity of the Codeine. I n the analysis of relatively pure .amples the codeine eluted from the column is colorless and cqrstalline, but with very impure mixtures such as opium, the (,luted codeine will vary from nearly colorless to light brown. Figure 5 is a graph of the weights of a series of frartions obtained in the analysis of a sample of opium plotted as a function of fraction number. After being weighed the eluted alkaloid fractions were dissolved in 95% ethyl alcohol and the absorbances of the resulting solutions were measured at wave lengths of 275 and 290 mp using a Beckman Model DU spectrophotometer. The iatio of the absorbance a t 275 to that a t 290 mp was computed for each fraction and these ratios are also plotted in Figure 5 The same ratio was determined for pure codeine, thebaine, neopine, and papaverine and theee values are shown in Table T'.
823 The melting point of the codeine in 1r:iction 23 waq 153 :3 to 154.5' C.. that of fraction 26 was 153.3' t u 154.5' C., and that of traction 27 was 149.4' to 151.0' C. The melting point of a .ample of codeine of Sational Formulary IX quality was 155.4' to 156.2' C. These data further confirm the purity and identity of t h e material eluted from the column. ACKNOWLEDGMENT
The authors wish to acknoirledge the contribution to this ~ o r k made by members of the Organic Research Department :ind Department of Chemical Control of the Mallinckrodt Chemical Korks who assisted in some of the experimental work dewrihcd :md n ho offered many helpful suggestions. LITERATURE CITED
Raizer, AI. 31.,Loter, A , , Ellner, K. S.,and Satriana, D. R.. J . Org. Chem., 16, 543 (1951).
Girard, P., Ann. pharm. f T a n G . . 8, 572~-3(1950). Homeyer, A. H., aiid Shilling, T V . I>...J. Org. Chem., 12, 356
Table V. Absorbance Ratios for Pure Allcaloids Alkaloid Codeine Thebaine Seopine Papaverine
(1947).
Nee. F. C., and Kirch, E. R., J . A w Pharm. Assoc., Sci. 42, 146 (1953).
Absorbance, 275/290 mp 0 897 i- 0 005 0 859 i- 0 005 1 29 i- 0 06 1 34 i- 0 05
El/.,
Kondo, H., J . Pharm. Soc. Japau. 57, 2118 (1937).
Levi, J. R..and Castelli, F., Arg7/ir. b i d . (Sao Paulo), 23, 2G3 (1939).
Levi, J. R., a,"d Cast$, F,.G a m . r h t r r t . ital., 68, 459 (1938). Sapara, V., Casopis CeskBho L 6 k d r u i c t i v . 63, 293-i (1950). Ptolman, A, and Stewart, C'. P., A ~ l a i y s t 74, , 536-42 (194ij. Stolman, A , , and Stewart. C . P.. I h i d . , 74, 543-6 (1947).
The ratios for the fractions in the codeine peak ale very close to that of codeine, and different from those of the probable impurities, indicating that the material is substantiallj- pure rodeine
Infrared Absorption Bands Characteristic of the Oxirane Ring W. A. PATTERSON' Central Research Laboratory, Canadian Industries, Ltd., McMasterville, Quebec, Canada
Part of the research program of this laborator) required the slntheses of a number of epoxy compounds. I n a follow-up of this program there was need for suitable methods for detecting these different compounds. Infrared spectroscopj appeared to offer the best hopes of success. This invol\ed a study of the infrared absorption spectra of the compounds. The infrared absorption of 26 epoxl compounds were recorded from 2 to 15 microns, in the liquid state and i n solution. The presence of a characteristic absorption band a t about 8 microns was confirmed and evidence compiled for two other characteristic absorption bands a t about 11 and 12 microns. The position of the latter bands \aried with the rompound, ranging from 10.52 (950 cm.-I) to 11.58 microns (863 cm.-l) in the 11.0-micron position and from 11.57 (864 cm.-l) to 12.72 microns (786 c m - l ) in t h e 12-micron position. Some correlation between the wa%e-lengthposition of t h e bands and the reartilit? of t h e compounds with acetic acid was noted. This rrork adds to t h e linowledge of the infrared ahsorption spectra of cpoxj compounds. I t also estahlishes the existence of characteristic infrared absorption bands for the epoxide ring i n t h e 10- to 13micron region. JIeretofore, e\idence of this had been limited. The correlation between t h e wave-length positions of the bands and t h e reacti\ities with acetic acid is of considerahle theoretical interest and of possible practical use.
.
A
S POIKTED out by Shreve, Heether, Knight, and Sn.ci,n
(8),little has been reported on the infrared spectra of heterocyclic oxygen compounds. They added materially, howwer, to the published data by reporting on the infrared absorption spectra of 13 oxirane compounds plus tetrahydropyran, tetrahydrofuran, and dioxane. Previous to this, Barnes, Gore, Liddel, :tnd Williams ( 2 ) had given a f e n spectra covering a limited range, and Field, Cole, and Woodford (3)had report)ed data on eight oxirane compounds. The lack of spectral data is reflected in the fact that little is known about absorption bands which are characteristic of thtx epoxide ring (oxirane group). Herzberg ( 5 ) , using the results of Linnett, has discussed the infrared and Raman spectra of ethylene oxide and found that there are three wave lengths attributable to the oxygen ring-at 7.92, 11.56, and 12.38 microns (1262, 865, and 808 cm.-l). Lespieau and Gredy (6) and Ballaus and Wagner (1) studied the Raman spectra of a number of simple epoxy compounds and found that the Raman shift a t 1262 em.-' (corresponding to infrared absorption at 7.02 microns) xas constant, while the spectra in the TOO- to nOO-cm.-l region (13 to 11 microns) were so compiicated that it was not possible to assign any frequency with certainty. Field, Cole, and Woodford (3) using the infrared apparently found similar conditions, as they concluded that only the %micron (1250-cm.-') band could be identified with reasonable certainty. Robinson in 1948 in thie laboratory recorded the spectral region a t about 8 microns for 19 oxirane compounds and showed that there mas a strong ah1
Present address, Baird Associates, Inc., Cambridge, Mass.
