DETERMINATION OF ALDEHYDES AND KETONES

4. DETERMINATION OF ALDEHYDES AND KETONES

Of the many procedures which have been suggested for the determination of aldehydes and ketones, only four general methods have attained practical significance. These are the bisulfite method, the neutral sulfite method, the phenylhydrazine method, and the hydroxylamine methods.

a. BisulfiteMethod. 

The bisulfite method is an absorption process based upon the general reaction:70
bisulfite method is an absorption process based upon the general reaction
Upon shaking a measured quantity of oil with a hot aqueous solution of sodium bisulfite, an addition compound71 forms which is generally water soluble and which dissolves in the hot bisulfite solution; the nonaldehyde
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70 There exists some question as to the linkage of the SO3Na group to the C atom of the carbonyl group ; this linkage may occur through the S atom or possibly through the O atom.
71 In many cases, this addition compound is a water soluble sulfonate instead of (or in addition to) the normal bisulfite addition compound of the carbonyl group. See p. 282.
Cassia flasks

results obtained are volume percentages. These methods are applicable only to oils containing large amounts of aldehydes or ketones. Watersoluble sulfonates may be formed from noncarbonyl compounds having double bonds; these will interfere with the accuracy of the analytical results. 73
The bisulfite method suffers from further disadvantages. There is no definite indication when all of the aldehyde has completely reacted. Although satisfactory for most aldehydes, the method is not suitable for the. determination of such ketones as carvone, thujone, pulcgone, menthone, fenchone, or camphor.
Procedure:74 Into a 150 cc. cassia flask, having a thin neck graduated in 0.1 cc. divisions, introduce 75 cc. of a freshly prepared, saturated, aqueous solution of sodium bisulfite,75 measured from a graduated cylinder. Pipette exactly 10 cc. of the oil into the flask. Upon thorough shaking, a semisolid mass frequently will result. Immerse the flask in a beaker of boiling water and occasionally shake until the solid addition compound has gone completely into solution. Shake the flask repeatedly to assure complete reaction of the aldehyde with the bisulfite solution. A further addition of 25 cc. of bisulfite solution is made, and the flask is again repeatedly shaken. After standing undisturbed in the beaker of boiling water for 10 min. to permit the unreacted oil to rise to the surface, add sufficient sodium bisulfite solution to force the unreacted oil into the neck of the flask. Any droplets of oil adhering to the sides are made to rise into the neck by gently tapping the flask, and by rotating it rapidly between the palms of the hands. After cooling the flask to room temperature, measure the amount of unreacted oil.
The aldehyde content may then be calculated by means of the following; formula :
Percentage of aldehyde = 10(10 - no. of cc. of unreacted oil).
As mentioned above, this result is a volume percentage. It may be converted into a weight percentage if the specific gravity of the original oil and of the aldehyde is known :
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73 In this connection, sec Dodge, Am. Perfumer, May (1940), 41. According to this authority only small amounts of unsaturatcd alcohols will dissolve if the solution of NaHSO3 is stronger than molar (10.4 per cent).
74 Variations of this procedure have been suggested by other authorities. Gildemeister and Hoffmann ("Die atherischen Ole," 3d Ed., Vol. I, 739) suggest the use of a 30 per cent aqueous solution of sodium acid sulfite which does not contain too much free sulfurous acid; if necessary the solution should be neutralized with sodium carbonate. It has been the experience of the laboratories of Fritzsche Brothers, Inc., that a freshly prepared solution of NaHSO3 made with Analytical Grade of reagent does not contain sufficient free H2SO3 to interfere with the reaction ; the separation of the noncarbonyl portion of the oil is sharper and more complete if a saturated solution of NaHSO3 is employed instead of a 30 per cent solution.
76 At room temperature, this will be approximately a 40 per cent (wt./vol.) solution. 
oil and of the aldehyde is knownof aldehyde or ketone \ Percentage by weight

After cooling to room temperature, a small amount of the bisulfite add tion compound will often precipitate out of solution, sometimes forming a the surface where the oil and aqueous layers meet; this renders an exact reading difficult. The addition of a few drops of water (added with medicine dropper in such a way that the water runs down along the inside of the neck of the flask), which will remain temporarily on top of the bisu fite solution, gives a sharp separation of the oil and aqueous layers. If the oil contains heavy metals, these should be removed before the determination by shaking the oil thoroughly with a small amount (about 1 per cent) < powdered tartaric acid and filtering; a sharper separation of the noncarbonyl layer will then result.
The procedure described above will prove satisfactory for those aldehydes which form water-soluble sulfonates in addition to the normal bisulfit addition compound e.g., citral, citronellal, 76 cinnamic aldehyde.
For aldehydes which form only the normal addition compound (e.g compounds which have no double bonds other than those present in the carbonyl group or benzene ring) but which form water-soluble bisulfite addtion compounds, the procedure must be modified. For the determination of phenylpropyl aldehyde,77 benzaldehyde,78 and anisic aldehyde, use a 10 cc sample and only 50 cc. of the saturated bisulfite solution. The normal addition compound which forms usually will not dissolve in the saturate bisulfite solution even after heating; consequently the flask should be fille by the addition of 25 cc. portions of water79 (instead of bisulfite solution After each addition, the flask should be thoroughly shaken and then in mersed in the boiling water for a period of about 5 min. The addition compound slowly dissolves and the nonreacting oily layer is driven into the neck of the flask and measured. Upon cooling and standing, some of the addition compound may settle out of solution. However, a reading usually may be obtained.
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76 In the determination of citronellal, the addition compound will often separate upon cooling; hence the reading should be taken as soon as the neck of the flask has cooled 1 room temperature.
77 In the determination of phenylpropyl aldehyde, considerable amounts of the additic compound separate upon cooling; however, a reading is possible.
78 Use is made of the poor solubility of the benzaldehyde addition compound in saturab NaHSO3 solution for the detection of benzaldehyde in cinnamic aldehyde; cinnamic aldhyde forms a sulfonate which dissolves completely in saturated NaHSOj solution. Hene the separation of a solid addition compound upon cooling the contents of the flask to room temperature is indicative of the presence of benzaldehyde.
79 Gildemeister and Hoffmann ("Die atherischen Ole," 3d Ed., Vol. I, 740) also recomend additions of water instead of NaHSO3 solution for the determination of benzaldhyde, anisic aldehyde, and phenylacetaldehyde.

In general, this modified procedure will not be satisfactory for the determination of decyl aldehyde,80 cuminic aldehyde, 81 methyl heptenone, 82 or phenylacetaldehyde which has polymerized. 83

b. Neutral Sulfite Method. 

This is also an absorption method. Using a neutral sufite solution, sodium hydroxide is liberated as the reaction proceeds; this must be periodically neutralized with acid to permit the reaction84 to go to completion. 
Neutral Sulfite Method

Although this method suffers from the disadvantages of an absorption process, nevertheless it offers certain advantages over the use of the bisulfite technique. Through the use of phenolphthalein, the exact end point of the reaction may be determined. Furthermore, some ketones react with neutral sulfite completely, so that this method may be used for their determination; this is specifically of importance for the determination of carvone in spearmint, dill, and caraway oils, of pulegone in pennyroyal oil, and of piperitone in eucalyptus oils. Carvone reacts smoothly requiring about 1 hr. for the determination The reaction with piperitone and with pulegone is very slow : only a 5 cc. sample should be used and the flask should be heated in a bath of vigorously boiling water.
Procedure: Into a 150 cc. cassia flask, having a thin neck graduated in 0.1 cc. divisions, introduce 75 cc. of a freshly prepared, saturated, aqueous solution85 of sodium sulfite, measured from a graduated cylinder. Add a few drops of a 1 per cent alcoholic phenolphthalein solution and neutralize the free alkali with a 50 per cent (by volume) aqueous acetic acid solution. Then pipette exactly 10 cc. of the oil into the flask and shake thoroughly. Immerse the flask in a beaker of boiling water and shake repeatedly. Neutralize the mixture from time to time
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80 Upon cooling, the entire contents of the flask will solidify making a reading difficult.
81 The addition compound formed is not sufficiently soluble even when the flask is heated.
82 The reaction with methyl heptenone is incomplete under the condition of the determination. M The nonaldehyde portion settles to the bottom of the flask. Reclaire (Perfumery Essential Oil Record 12 (1921), 341) recommends the use of a special flask for this determination. The hydroxylamine method (see p. 285) will prove entirely satisfactory. M See footnotes 71 and 72, p. 279.
86 At room temperature this will be approximately a 30 per cent (wt./vol.) solution.

with the 50 per cent acetic acid.86 Continue this procedure until no further pink color appears upon the addition of a few more drops of phenolphthalein solution. Permit the flask to remain in the boiling water for an additional 15 min. to assure complete reaction. Then add sufficient neutralized sodium sulfite solution to raise the lower limit of the oily layer within the graduated portion of the neck. Any droplets of oil adhering to the sides are made to rise into the neck by gently tapping the flask, and by rotating it rapidly between the palms of the hands. After cooling the flask to room temperature, measure the amount of unreacted oil. The aldehyde content may then be calculated by means of the formula given under bisulfite method.
The neutral sulfite method is the official method of "The United States Pharmacopoeia" for the determination of cinnamic aldehyde in cassia oil,87 for carvone in spearmint oil,88 and of "The National Formulary" for carvone in caraway oil.89 It proves satisfactory for the determination of citral in lemongrass oils,90 the reaction being very rapid.
As in the case of the bisulfite method, oils containing heavy metals should be treated with tartaric acid before a determination is attempted (see p. 311).

c. Phenylhydrazine Method

The phenylhydrazine method is seldom used today. It attained importance as the first practical method for the assay of citral in lemon oil.91 The official method of "The United States Pharmacopoeia," Tenth Revision, is included here, since commercial contracts occasionally specify that aldehydes be determined by the phenylhydrazine method.
An accurately measured amount of an alcoholic solution of freshly distilled phenylhydrazine is added to a weighed amount of the oil. The excess of phenylhydrazine is titrated with hydrochloric acid. A blank is run simultaneously, and from the difference in the amounts of standardized hydrochloric acid required for the blank and the determination, the percentage of aldehyde is calculated.
RCHO + C6H5NNH2 -> C6H5NX = CHR + H2O
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86 "The United States Pharmacopoeia," Thirteenth Rev., 132, suggests neutralization with a 30 per cent NaHSO3 solution. However, the volume of solution frequently becomes too great to permit thorough shaking.
87 Thirteenth Revision, 132.
88 Thirteenth Revision, 510.
89 Eighth Edition, 121.
90 See footnote 72, p. 280.
91 This method was first proposed by Kleber, Am. Perfumer 6 (1912), 284.
The method, as described, is suitable for the determination of aldehydes in the citrus oils.
Procedure:92 Place about 15 cc. of oil of lemon in a tared, 250 cc. Erlenmeyer. flask, and weigh accurately. Add 10 cc. of an alcoholic solution of phenylhydrazine93 (1 in 10) (not darker in color than pale yellow), and allow it to stand for 30 min. at room temperature. Then add 3 drops of a 0.1% aqueous solution of methyl orange, and neutralize the liquid by the addition of half-normal hydrochloric acid. If difficulty is experienced in determining the end point of the reaction, continue the titration until the liquid is distinctly acid, transfer it to a separatory funnel, and after the layers have separated draw off the alcoholic portion. Wash the oil remaining in the funnel with distilled water, adding the washings to the alcoholic solution, and titrate the latter with half-normal sodium hydroxide. Carry out a blank test identical with the foregoing, omitting the oil of lemon, and note the amount of half-normal hydrochloric acid consumed. Subtract the number of cc. of half-normal sodium hydroxide from the number of cc. of half-normal hydrochloric acid consumed in the test containing the oil of lemon, and this result from the number of cc. of half-normal hydrochloric acid consumed in the test without the oil of lemon. Each cc. of this difference corresponds to 0.07609 g. of aldehydes calculated as citral.
In the case of orange oils, the aldehyde is usually calculated as decyl; the factor then used is 0.07813. In the case of grapefruit oils, the aldehydes are frequently calculated as an equal mixture of octyl and decyl; the factor then used is 0.07112.
The results obtained in the above method represent percentages by weight.

d. Hydroxylamine Methods. 

Two important techniques have been developed, both based upon the use of hydroxylamine for the determination of aldehydes and ketones. The first makes use of a solution of hydroxylamine hydrochloride and the subsequent neutralization with standardized alkali of the hydrochloric acid liberated by the reaction. The second technique makes use of a solution of hydroxylamine (i.e., a solution of the hydrochloride with substantially all of the combined hydrochloric acid previously neutralized with alkali) ; after the reaction with the aldehyde or ketone, the mixture is titrated with standardized acid. The latter procedure is known as the Stillman-Reed method. Both modifications are based
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92 "The United States Pharmacopoeia," Tenth Revision, 260.
93 The phenylhydrazine solution should be measured accurately from a pipette or burette.
upon the fundamental reaction : 
Hydroxylamine Methods

The hydroxylamine methods offer many advantages over the absorption processes. Relatively small amounts of the oil are required for a determination. The reaction of hydroxylamine with aldehydes is rapid, shortening the time required for a determination. Water-soluble adulterants which do not contain a carbonyl group do not analyze as apparent aldehyde or ketone. The methods have proved satisfactory for the determination of certain ketones (such as menthone and thujone) which cannot be determined conveniently by the absorption procedures. In fact, hydroxylamine will react with practically all aldehydes and most ketones encountered by the essential oil chemist. Furthermore, these hydroxylamine methods prove exceptionally applicable to oils which contain only small amounts of aldehydes or ketones (e.g., lemon oils), and to oils containing large amounts of free acids (e.g., orris oils). The solutions used for the standard procedure are stable and can be kept for many months; however, the Stillman-Reed solution deteriorates rapidly and is best prepared when needed.
The hydroxylamine methods have certain disadvantages not inherent in absorption techniques. It must be remembered that the calculation of results involves the molecular weight of the aldehyde or ketone, giving percentages by weight; hence adulterations with carbonyl compounds of lower molecular weight give apparent percentages which are too high. If more than one aldehyde or ketone is present in an oil, all are calculated as a specific carbonyl compound. Since the reaction of hydroxylamine is quite universal, it is difficult to determine an individual component. Nor can the carbonyl and noncarbonyl portions be separated conveniently and studied individually.
Standard Procedure:94 Into a 100 cc. saponification flask weigh accurately the requisite amount of oil or synthetic and add 35 cc. of 0.5 N hydroxylamine hydrochioride solution, measured from a graduated cylinder. Permit the flask to stand at room temperature for the proper length of time and titrate the liberated hydrochloric acid with standardized 3.5 N alcoholic sodium hydroxide. The titration is continued until the original greenish shade of the hydroxylamine solution is obtained. A second flask containing 35 cc. of hydroxylamine hydrochloride solution may be used as a blank to assure a more accurate color match.96
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94 This is essentially the procedure described in "The United States Pharmacopoeia," Twelfth Revision, 314, for the determination of benzaldehyde in bitter almond oil.
Percentage of aldehyde or ketone =am/20s
where : a = number of cc. of 0.5 N sodium hydroxide used for neutralization;
            m = molecular weight of the aldehyde or ketone;
            s = weight of sample in grams.
Preparation of 0.5 N Hydroxylamine Hydrochloride Solution: Dissolve 275 g. of recrystallized hydroxylamine hydrochloride96 in 300 cc. of distilled water; warm to a temperature of 65 on a steam bath to yield a clear solution. Add this solution slowly to 2 gal. of 95% alcohol, and mix thoroughly. Then add 125 cc. of a 0.1% solution of bromphenol blue indicator in 50% alcohol, and sufficient 0.5 N alcoholic sodium hydroxide solution to change the yellow color of the solution to a greenish shade; this usually requires about 20 to 25 cc. of the alkali. The proper degree of neutralization is attained when 35 cc. of the solution shows a distinct greenish shade which changes to a distinct yellow upon the addition of 1 drop of 0.5 N hydrochloric acid. A stable solution of hydroxylamine hydrochloride is thus obtained which is approximately 0.5 N ; an exact adjustment is unnecessary.
For lesser quantities of solution, dissolve 34.75 g. of recrystallized hydroxylamine hydrochloride in 40 cc. of distilled water and make up to 1 liter with 95% alcohol; add 15 cc. of the bromphenol blue solution and neutralize.
The proper size of sample and the proper length of time to give complete reaction and the molecular weights of the most frequently encountered aldehydes and ketones are given in Table 4.12.
Stillman-Reed Procedure:97 Proceed as directed under the standard procedure but add 75 cc. of hydroxylamine solution, measured accurately by means of a burette or pipette. At the same time run a blank determination. After standing the required length of time, titrate with standardized 0.5 N hydrochloric acid to a green-yellow end point. Care should be taken to titrate both the blank and the sample to the same end point. Calculate the percentage of aldehyde or ketone as described above.
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96 In the case of very darkly colored oils, the size of sample should be greatly reduced and the end point determined with the aid of a spotplate. This is particularly important in the case of oils which have a greenish color e.g., wormwood oils.
96 The hydroxylamine hydrochloride offered by Commercial Solvents Corp. under the name of "hydroxylammonium chloride" is sufficiently pure, after recrystallization from water, for the preparation of this solution.
97 Perfumery Essential Oil Record 23 (1932), 278.
 TABLE 4.12. MOLECULAR WEIGHTS* AND REACTION TIME OF ALDEHYDES AN KETONES.
PART I
 MOLECULAR WEIGHTS AND REACTION TIME OF ALDEHYDES AN KETONES.

TABLE 4.12 (cont.)

 MOLECULAR WEIGHTS AND REACTION TIME OF ALDEHYDES AN KETONES.1

 TABLE 4.12 (cont.)

 MOLECULAR WEIGHTS AND REACTION TIME OF ALDEHYDES AN KETONES.2

Preparation of 0.5 N Hydroxylamine Solution: Dissolve 20 g. of recrystallized hydroxylamine hydrochloride in 40 cc. of water and dilute to 400 cc. with 95% alcohol. To this solution, in a 1 liter beaker, add, with stirring, 300 cc. of 0.5 N alcoholic potassium hydroxide and 2.5 cc. of a 0.4% bromphenoi blue solution in 50% alcohol. Permit the solution to stand for 30 min. and filter. This solution cannot be stored for any appreciable period. A blank must always be run since the solution tends to deteriorate slowly.
In conclusion it might be well to point out that each of the general methods for the determination of aldehydes and ketones has its place in the analysis of essential oils. Thus, absorption methods permit of the easy separation of the noncarbonyl portion of the oil and of the separation of some aldehydes and ketones by regeneration from the bisulfite addition compound with strong alkali. It then becomes possible to study the odor and other properties of these individual portions and to detect more readily adulteration of the original oil. A comparison of the results from the absorption methods and from the hydroxylamine method is frequently very revealing; large differences may be indicative of adulteration with watersoluble constituents or additions of carbonyl compounds of low molecular weight.
From a consideration of the limitations of each method, it should be obvious that it is of utmost importance always to record the method used when reporting an analytical result.

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