T H E J O U R N A L OF I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y
610
e = height of column (mm.) of standard used for comparison, f = height of column (mm.) of unknown used for comparison. a X c X e X IOO Then = per cent citral in oil or exb X d X f tract. EXAMPLE-Lemon oil weighed 0.5384 g. Preliminary d = 5 cc., e = 86 mm.,. _f = 11 . . mm. 0.002 X 50 X 86 X I O O = 4.25 per cent, and 0.5384 x 5 x 7 7 7 7 = 4.47 cc. approximate amount of 1st dilu5 cc. X 86
tion t o be used in final determination. Final d = 4.5 cc., e = 7 9 mm., f = 7 7 mm. 0.002
x
50
x
79
x
IO0
= 4.23+ per cent. 0.5384 x 4.5 x 7 7 u.s. FOODAND DRUGINSPECTION 1,ABORATORY DENVER, COLORADO
THE IDENTIFICATION AND DETERMINATION OF POTASSIUM GUAIACOL SULFONATE B y SAMUEL PALKIN Received June 1, 1918
The sulfonic acid salt of guaiacol has been used in medicine for a numbar of years. When so employed it is practically never used by itself but in conjunction with gums, resins, alkaloids, and other medicinal agents t o counteract various symptoms. This renders its identification and determination much more difficult t h a n if the substance were used alone. Many wellknown qualitative tests for common elements are thus rendered almost useless b y the presence of ordinary resins and other complicating substances t h a t are generally present in medicinal preparations. The potassium guaiacol sulfonate' used in medicine is apparently the metasulfonic acid2 salt of guaiacol. It is a colorless salt, very soluble in water, only slightly soluble in alcohol and insoluble in ether, bznzene, and chloroform. Two samples of potassium guaiacol sulfonate from different manufacturers were obtained in the open market. These samples are designated A and B in the paper. EXPERIMENTAL
As stated in the patent of F a b r i k - H e ~ d e n ,no ~ insoluble salts of the sulfonate were obtained with the heavy metals, with the exception of lead subacetate in the neutral or alkaline solution. As the compound is most generally accompanied by resins and othzr substances precipitable b y lead subacetate, this reagent could have but little value in this connection. Organic bases gave no insoluble compounds. N o good solvent was found which would extract guaiacol sulfonic acid. Amyl alcohol does so t o some extent, but has not been found of value. Taking advantage of the phenolic properties of this compound, the action of chlorine and bromine was tried. Very little action occurs in the concentrations 1 D. R . P. 109,789, Friedlander, V (1900), 738; D. R . P. 188,506, Friedlander, VI11 (1907), 936. 2 I,. Paul, Ber.. 39 (1906), 2773, 4093; A. R!sing, I b i d . , 89 (1906), 3685 8 LOC.
C i l . (2).
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of the compound generally used, but in higher concentrations the dibrom guaiacol sulfonate1 is formed. This compound is extremely soluble in water and quite insoluble in most organic solvents. As i t has no , definite melting point or other easily identifiable physical or chemical property, the formation of this compound&was not found t o be of any use for the purpose in hand. In the presence of strong hydrochloric acid and with heat, a rather unexpected reaction takes place. Instead of mere formation of a chlor- or brom-compound, hydrolysis takes place, sulfuric acid being split off almost completely and but a very small amount of chlor- or brom-compound is precipitated, and t h a t apparently of guaiacol itself. T h a t guaiacol is a n intef-mediate compound is made apparent by the fact t h a t i t can readily be detected by its odor during the process of heating. This is especially true when a dilute chlorine solution is used. The amount of halogen compound formed is very small and is furthermore contaminated by other by-products, thus making i t useless for purposes of identification. So effective, however, is the halogen (bromine in particular) in its hydrolytic action on the sulfonate that nearly 97 per cent of the theoretical amount of sulfuric acid is thus obtainable. I n fact, this procedure with some modification is actually made use of subsequently in the quantitative determination of this compound. Another and rather useful reaction depending on t h e . phenolic properties was found in the coupling of this compound with diazotized amipes. Among those tried were aniline, toluidine, xylidine, tolidine, 0 - and #-nitro anilind, p-amido phenol and naphthylamine, and a n azo dye was formed in practically every case; ' b u t in nearly all cases, a dirty brown precipitate, exceedingly voluminous and not particularly characteristic, resulted, with the exception of t h a t obtained with p-nitro aniline. The diazotized p-nitro aniline gave, with the alkali guaiacol sulfonic acid, a dark red, water-soluble dye, which behaved as a n indicator. A small quantity of the dye used as an indicator changes very sharply from red in the alkaline solution t o yellow in the acid solution. The dye is only slightly solubl: in chloroform and ether but very readily soluble in amyl alcohol. I n the presence of various contaminating substances as mentioned above, this dye can be extracted from the water (acid) solution with amyl alcohol and with alkali re-extracted from the amyl alcohol, thus rendering i t free from obscuring impurities and observing clearly t h e color changes. It is necessary t o eliminate or establish the absence of phenols, or guaiacol itself, which also give red dyes when applied as coupling agents t o diazotized p-nitro aniline. Since guaiacol sulfonic acid is nonvolatile with steam and cannot ordinarily be shaken out b y organic solvents, preliminary treatment t o insure t h e absence of other interfering phenols can readily be resorted t o before applying the reaction. HYDROLYSIS--AS pointed out in the discussion of ,the action of halogen on this compound, instead of the I
Krauss and Krede, J . A m . Chem. Soc., 39 (19171, 1432.
Aug., 1918
T H E JOCR,VAL O F I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y
expected halogenation, there results the hydrolytic action yielding sulfuric acid. The usual procedure of heating with hydrochloric acid in a sealed tube was resorted io. About I O O mg. substance was heated with concentrated HCl in a sealed tube to z o o o C. for several hours. Some charring took place but most of the sulfuric acid was split off and some of the guaiacol was further attacked t o forin pyrocatechol as indicated by a number of corroborative tests. A quantitative determination showed t h a t about 88 per cznt of th3 guaiacol sulfonate was converted. The use of t h e sealed tube is, of course, attended with some difficulty and quite inapplicable t o preparations t h a t generally contain guaiacol sulfonate. The experimznt was made merely t o note approximate extent of hydrolysis and products formed. A procedure involving the same principles, viz., high temperature, strong acid, and a t the same time presence of moisture, was found in t h e use of high boiling liquids as well as salt solutions. These accomplished the same results much more readily. Best results were obtained with phosphoric acid (containing some NaC1) and with a concentrated ZnClz and HC1 solution which ultimately boils at abouz 2 0 0 ' C. The characteristic odor of guaiacol is given off during the boiling, if interfering substances are not present, and the volatile phenol can be distilled over and tested for in the usual manner. A color change t o wine-red and then t o brown or charring is observdd in t h e latter stages of the boiling. Attempt was made t o utilize either phosphoric acid or zinc chloride for t h e quantitative conversion'of t h e sulfonic acid t o sulfate. Nearly quantitative results were obtained with ZnCls, b u t the results were nearly always somewhat low, owing, apparently, t o the reduction of some of the sulfuric acid during charring. Oxidation with a few drops of nitric acid during boiling was tried but was found t o cause formation of pitro compounds (apparently picric acid), which precipitated along with t h e barium sulfate and invariably gave high results on ignition. Owing t o t h e tendency of phosphates t o be dragged down with the precipitates in t h e determination of sulfates, t h e results, using phosphoric acid as the hydrolytic agent, were always high. This procedure, while useful for qualitative purposes, was, therefore, deemed undesirable for quantitative determinations. A table follows which shows results obtained by the various procedures described above. The two samples of potassium guaiacol sulfonate used were previously analyzed b y the bomb ignition methods as follows: A weighed amount of sample not exceeding 1 5 0 mg. mixed with a n equal amount of sulfur-free benzoic acid was inserted in a Parr calorimeter bomb, about 5 g. C. P. sodium peroxide added, the whole mixed and ignited, and the sulfates determined in the usual manner, with the following results: Per cent SOs Sample A . .
.............................
Sample B . .
...........................
i
(a)31.6 ( b ) 31.2 (c) 31.4
TABLEOF RESULTS Weight Sample Mg. Reagent used 100 100
100 100 100 100 100
100
100 100 100
100
"Os Conc. (No bromine) fhTobromine)
ZnClz ZnClz ZnCh
100 100
ZnClz ZnClz
100
ZnClz drops of "0s (Br HNOa 4-Br)
"03
100
1 2
3 4
+ drops of +
+
Sugar syrup added None None None None None None None None None None None None None
611
so3 SO8 by found bomb method G.
G.
0.0308
0.03 141 O.O314(c) 0.0304 0,0302 0.0314 0.0303 0.0311 0.0308 0,0291 0.0280 0.0300 0.0301 0.0314 0.0294 0.0314 0,0284 0.0314
None
0.0324
0.0314
None
0.0336
0.0314
0.0314 0.0315 0.0318 0.0315 0.0319
0.0314 0.0314 0.0314 0.0314 0.0314
None 100 None None IO0 None 100 Proposed method None 100 Proposed method 5 cc. Conc. 100 Proposed method Syrup 100 Proposed method 5 cc. Conc. 100 Proposed method Syrup 5 cc. Conc. 100 Proposed method Syrup 5 cc. Conc. 100 Proposed method Syrup 5 cc. Conc. 200 Proposed method Syrup 5 cc. Conc. 250 Proposed method Syrup 5 cc. Conc. 2 00 Proposed method Syrup 5 cc. Conc. 100 Proppsed method Syrup 5 cc. Conc. 100 Proposed mcthod Syrup 5 cc. Conc. 225 Proposed method Syrup Average'of 3 determinations of B. Calculated from average of B. Average of 3 determinations of A. Calculated from ( 3 ) .
0.0316
0.0314
0 0315
0.0314
0.0318
0.0314
0.0315
0.0314
0.0622
0.06282
0.07855 0.07852 0.0631
0.06282
0.03074 0.03073 0 0306
0.03073
0 0692
0.06914
The following method for thz qualitative testing and quantitative determination of potassium guaiacol sulfonate is recommended, with the view to its adaptation t o the medicinal preparations in which it is most likely t o occur. It must be borne in mind t h a t other sulfur-bearing compounds such as sulfonal, trional, saccharine, etc., must either be proven t o be absent or, if present, previously removed by extraction before applying the method described. The author knows of no other sulfonic acids employed in medicine except ichthyol and the rarely used phenol sulfonates. The quantitative procedure herein described will not be accurate in t h e presence of those compounds. The qualitative tests are not interfered with by ichthyol, as nearly all of the ichthyol is precipitated on acidification with hydrochloric acid as directed in the method, the free sulfonic acid of t h a t compound being very difficultly soluble in water. The phenol sulfonates are readily converted into the insoluble tribrom phenol by the action of bromine. QUALITATIVE-(a)Some of the sample containing potassium guaiacol sulfonate is diluted with water and acidified with hydrochloric acid. If a resinous or other precipitate comes down, it is filtered. A portion of t h e filtrate {s tested for sulfate. Another portion of the filtrate is made more strongly acid with HC1 after the addition of a few grams of sodium peroxide. The solution is boiled and chlorine is generated in limited quantities which attacks the guaiacol sulfonic acid. I n the presence of this compound, t h e characteristic odor of guaiacol becomes perceptible. If, after boil-
612
T H E J O U R N A L OF I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y
ing for about 1 5 t o 2 0 min., a precipttate is formed, this is filtered off and the filtrate nearly neutralized with sodium hydroxide and tested for sulfates. Commercial hydrogen p2roxide contains sulfates and naturally cannot be used for t h a t test. I n the a b s a c e of sulfate in the original sample, and subszquent formation of sulfate by the action of the chlorine, a good indication is had of the presence of sulfonic acid.guaiacol. I n the presence of sulfate in the original, determination of sulfates before and after have t o be resorted to in order t o note increase due t o sulfonic acid. ( b ) Some of the filtrate is made alkaline and t o it is added drop by drop a c o l b solution of diazotized p-nitro aniline. (The diazo salt is prepared by dissolving 140 mg. p-nitro aniline in 8 cc. H z O and I or 2 cc. concentrated HC1, cooling and adding 7 5 mg. sodium nitrite dissolved in a few cc. of HzO.) I n the presence of guaiacol sulfonate the solution will be colored deep red. If substances are present which obscure the color, the solution is made acid with HC1, extracted in a separatory funnel with amyl alcohol, t h e lower aqueous layzr is tapped off, and the alcohol layer re-extracted with NaOH solution, when t h e azo dye will cblor the aqueous layer deep red. On acidification, t h e solution changes very sharply t o yellow, the aao dye behaving like a n indicator in t h a t respect. If guaiacol or other phenols are present in t h e original solution, they should be removed beforehand by steam distillation or extraction with organic solvent as t h e case may require. The guaiacol sulfonic acid will remain behind and can subsequently be tested for as indicated above. (c) I n the absence of much organic material or possible removal of the same the following procedure may be used. To a concentrated solution of t h e sample ( a few cc.) in a hard glass test tube are added about 5 cc. syrupy phosphoric acid containing a little NaC1, and the mixture is boiled or preferably distilled over. Distillate, which may be less than I cc., may then be tested for the presence of guaiacol and pyrocatechol, as both are generally formed. A few drops of a very dilute ferric chloride solution will give with the distillate (in the absence of much HCI) a green coloration which changes t o yellowish and on addition of ammonia changes t o violet-blue. The neutral, or better, ammoniacal solution causes marked reduction of silver nitrate. QUAKTITATIVE DETERMINATION-(Q) I n the absence of much contaminating matsrial, a known amount of the sample, which should not contain much more than 2 0 0 mg. of potassium guaiacol sulfonate, is diluted somewhat with water in a 1 5 0 t o 2 0 0 cc. Erlenmeyer flask and I O t o 2 0 cc. concentrated HC1 are added and then a few cc. liquid bromine. The solution is boiled gently and bromine added several times. It is then evaporated down t o a small volume on the steam bath, using air blast, I O cc. concentrated " 0 3 added, and some more bromine and boiled. This is done to convert the last traces of sulfonic acid guaiacol. The process is repeated twice and the whole evaporated t o
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dryness on the steam bath. It is then diluted with water and sulfates determined in the usual manner. ( b ) I n the przsence of much organic material, which is most often the case, a weighed quantity of the sample in a 1 5 0 cc. Erlenmeyer flask is treated repreferably fuming peatedly with concentrated " 0 3 , "03, heating gently a t first until nearly all of the organic material has been oxidized. The samz process is then repeated, using bromine and concentrated "03, several times. The whole solution is then evaporated t o dryness on the steam bath and the sulfates determined as above.
-
Factor for conversion of Bas04 to SO, = 0.3428; factor for conversion of Bas04 t o potassium guaiacol sulfonate 1.0376. BUREAUOF CHEMISTRY OF AGRICULTURE DEPARTMENT WASHINGTON, D . C.
THE OCCURRENCE OF CAROTIN IN OILS AND VEGETABLES By AUGUSTUSH. GILL Received April 5, 1918
I n a previous paper' i t was shown t h a t the peculiar bluish reaction of palm oil was due t o carotin, and t h a t palm oil could not be detected in oleomargarine by this test, because the animal fats also contained carotin. A t t h a t time, the subject was being further studied, as t o what other fats and oils might contain it. As the carotin is undoubtedly dissolved out from the seeds by the oils they contain, and as it is present in them in extremely small amounts, it was deemed best t o extract it from the seeds, rather t h a n from the oils 8 themselves. The substances investigated were: ( a ) Seeds: Yellow corn, flax, mustard, black sesame, rape, and white sunflower. ( b ) Yellow colored vegetables or products: Carrots, squash, turnip, orange peel, safflower, cottonseed meal, turmeric, and neat's-foot and linseed oils. The procedure used in isolating carotin from various oils and vegetables consisted in extracting the finely divided dried vegetable with carbon bisulfide a t a return flow condenser, .evaporating off the solvent, and saponifying the residue or oil with alcoholic sodium or potassium hydroxide, leaving a slight excess of alkali; t o ensure the absence of free oil, the alcohol was evaporated, keeping the temperature below 70' C. as much as possible. and the residual soap was then dissolved in water. The solution was shaken out with carbon bisulfide, which, in the presence of carotin, assumed a yellow or orange color, depending upon the amount of carbon bisulfide used. The carbon bisulfide was evaporated off, and the residue again treated with a n excess of sodium hydroxide t o ensure the complete removal of, any oil which might possibly have escaped saponification. The resulting soap solution was extracted with carbon bisulfide, as before, with similar results. Those vegetables t h a t were free from oils, such as carrots, were extractea directly with carbon bisulfide, after first drying the finely divided sample a t a low temperature. 1
THISJOURNAL, 9 (1917), 136.
