550
ANALYTICAL CHEMISTRY
(1952). (3) ~ ~ ~w, E, ~ lto t Standard ~ ~ oill co. , (Ind,)l,
cHEM., , 24, 1889 u, s, Patent
Chicago Section, . ~ M I E R I C A N CHEMICAL SOCIETY,one-day technical meeting, Jan. 24, 1947. (6) Podbielniak, h e . , Chicago, Ill., Bull. A-3 (1953). ( 7 ) Podbielniak, w.J., IND. ENG.CHEA~., ;INAL. ED., 13, 639-45 (1941). (8) Weissberger, A., “Technique of Organic Chemistry,” Val. IV, pp. 178 ff., Interscience, Xew York, 1951.
Ibid., 2,631,091(March 10, 1953). (5) Piros, J. J., and Glover, J. -4.(to Siriclair Research Laboratories, Inc.), I b i d . , 2,608,528(Aug. 26, 1952); paper presented before
R E C E I V E for D re\-iew LIay 26, l!15+, Accepted December 18, 1954 Presented before the 19th Midyear .\Ieeting of the Dirision of Refining, Anierican Petroleuni Institute, Houston. Tex., 1 I a s 1954.
LITERATURE CITED
(1) Donnell, C. K., and Kennedy, R. hf., I n d . Eng. Chem., 42,
2327-31 (1950). (2) Foster, N. G,, and G
~ L. E,, ~
jr,, ~ akN.4L. ~
2.661.938(Dee. 8., 1953). ~.~ (4) Kuentsel, W. E., and Field. E. [to Standard Oil Co. (Ind.)],
Determination of Carboxylic Amides by Reduction to the Corresponding Amine SIDNEY SlGGlA
and
C.
R. STAHL
Centra/ Research Laboratory, General Aniline
& Film
.i method is described for determining primary, secondary, and tertiary amides based on reduction of the amides to the corresponding amine using lithium aluminum hydride. The amine formed is steam-distilled from the reaction mixture and is then titrated with standard acid. The procedure was initially developed for determining sodium N-lauroyl sarcosinate (A\7lauroyl-N-methyl sodium glycinate). Once the procedure was established for this compound, it was tried on other samples of amides and found to work satisfactorily. The range of the method is large, extending from aliphatic amides of low molecular weight to the fatty amides. Other types of amides were also found to be determinable by the method. The accuracy and precision of the procedure are usually within =!=2Q/, and are often within &I%, depending on the particular amide.
T
H E nitrogen content of a sample has been used to deterniine amide content ( 1 , 3 - 5 , 1 1 , 1 2 , l 4 , 1 5 ) , but this approach lacks specificity for the amide grouping. H\-drolysis ( I S , 1 4 ) is mainly applicable only to some primary amides and is very seldom applicable to any secondary or tertiary amides, as these are rather difficult to hydrolyze. A colorimetric method has been devised (2) involving conversion of the amide to the corresponding hydroxamic acid and formation of the colored ferric chloride complex, which is measured colorimetrically. This method is escellent for determining small amounts of amides, but where the amount of amide compound in a sample is rather large (10 to loo%), a higher precision and accuracy than are obtainable by the colorimetric approach are generally needed. Mitchell and Ashby (8) determined primary amides by reaction with 3,5-dinitrobenzoyl chloride. Olleman ( I O ) , Iirynitskp ( 7 ) ,Hochstein ( 6 ) ,and Zaugg and Horrom (16) determined aniides via active hydrogen analysis. using lithium aluminum hydride among other reagents which react with active hydrogen atoms. These methods lack in specificity, as many organic compounds contain active hydrogen atoms, and tertiary amide groups do not. Nystrom and Brown ( 9 ) , in an article on reactions of lithium aluminum hydride, report that the reduction of amides proceeds to the formation of the corresponding amine: 2RCOh’Rz
+ LiAlH4
--*
2RCHzNRz
+ Li.4102
It was thought that an analytical method could be devised based on this chemical reaction, and the procedure described below was evolved. The method is based on reduction of the amide with the hy-
Corp., Easton,
pd.
dride and steam distillation of the amine formed. It was first thought that the amine formed could be titrated in the reaction mixture. It as supposed that one break would. be obtained for the strong bases (metal hydroxides) and a second break for the neaker base (amine). However, the results obtained by this approach were very high, probably becauee aluminum hydroxide is not so strong a base as was firrt supposed. I n view of these results, the steam distillation step was added to the analysis. I n the determination of fatty acid amides the corresponding amines formed on reduction steam distill very slowly; so ethylene glycol was used instead of n ater in the distillation. The glycol distillation is used for the determination of the
!
sodium S-lauroylsnrcosinate ( Medialan, C,H23 -NCH2COOXa).
I
CHa The amine formed in the reduction of this compound is distillable from a caustic solution (the Kjeldahl distillation). The sarcosinate contains a carboxyl group that in the resultant amine should be in the form of the salt in the alkaline solution. This amino acid salt should be difficult to distill. However, it is presumed that in the reduction step, the carboyyl group is reduced to the alcohol, so that the resultant amine n o d d be CllH2&H&CH2CH20H, which I
0
is distillable.
Amides of the type R&-NCH2CHzS08Na cannot
I
Ri be det,ermined by this method. Evidently the sulfonic acid group is not satisfactorily reduced, and the salt of the amine will not distill. Very low results are obtained on these compounds. This method is applicable to a large range of amides, as seen in Table I. Primary, secondary, and tertiary amides of low molecular weight acids and fatty acids, as well as difunctional amides, were successfully determined. . 4 cyclic amide (methyl pyrrolidone) was also determined. Unsatisfactory reduct,ions were noted for acrylamide, S-tert-butyl acrylamide, and urea. In the case of S,X-diphenyl acetamide, the resulting amine (diphenylethylamine) is too weakly basic to titrate, even in 801vents designed for titrating weak bases. hfany funct,ional groups react with lithium aluminum hydiide, but very few result in the formation of a volatile base. Nitriles, im’des, and alipfiatic nitro compounds are the only others which, to date, are known to form an amine on reduction with the hydride The aliphatic nitro compounds are rarely found in amide samples; nitriles are sonietinies found in samples of primary amides. Lithium aluminum hydride will reduce nitriles to the corre-
551
V O L U M E 2 7 , N O . 4, A P R I L 1 9 5 5 sponding amine, and this will result iii high values for the amide. T h e reduction of nitrile does not proceed to completion in all cases of nitriles; therefore, this would not be a good general method for nitriles. Benzonitrile, butyronitrile, capronitrile, and chlorobenzonitrile were determined satisfactorily by this approach (see Table 11). Nitriles which were tried and could not be reduced completely to amine in a convenient length of time were acetonitrile, acrylonitrile, succinonitrile, adiponitrile, phenylacetonitrile, 3-butenenitrile, 7-phenoxybutyronitrile, lactonitrile, m-nitrobenzonitrile, and 1-naphthonitrile.
Table 1. Results % 4a
Compound Acetyl diethylamine (.V, .V-diethylacetamidr)
99.2 98 1 98 2
by N 97 7
Procedure A
97.1
A
It is advisable, therefore, if nitriles are suspected in a sample of a primary amide, to use the procedure of Mitchell and Ashby (8) for determining the primary amide. Nitriles seldom occur in secondary and tertiary amides, so that possible interference is minimized.
98 4 98.4 K-butyramide
95.4
97.2 96.2 K-methyl acetamide
K-methyl pyrrolidone Aretamide Propionamide
?-FIvdroxybutramide
03 5
92.8 93.8 94.2 98.2 98.6 98.1 loo r, ino.8 100.3 101.1 100 8 100.3 100.0 100.0 96.3
9.5 2
A
97.8
A
49,S
A
100 4
4
96.1
4
Rlrtliyl glycolamide
m.0 95.8 9.5, fi
46.3
A
A- .\-'-dimethyl oxamide
9.5.2 95.4 O0.9
100.8
.4
Benaamide
99 8 94..5 99.8 98.5
100 8
A
100 6
.4
93.4
A
96.6
A
95 1
n
98 3
B
94.5
B
96 6
B
97.6
B
98.8
A
99.1
Ba
...
Be
95.8
BQ
Formamide Dinrethyl formamide Octanamide ITrsaderanamide
XIptlry1 stearamide
ion n
99.7 99.0 98.9 98.6 90.7 89.5 92.2 96.4 98.1 47.5 95 2 94 H 94 6 94 9 97 4 98 fi
ion n Fteaiamide Dodecanamide AlPtIiyl dodecanamide Surcinimide
98 0 92 4 92.7 93.7 96.0 95.8 94.2 94.4 92 3 93.1 99 3
Sodium S-lauroyl sarcosinate Sodium S-lariroyl sarcosinatee
lOL.5 100.2 100.3 99.8 30 27 30 11 30 0 4 94.7 93.7 93.7 94.6 94.4
Reflux time forrreduction step was increased t o 1.5 hours for these compounds. b A 30% aqueous solution of sodium A-lauroyl sarcosinate. Each sample was dried at looo C. before reduction C Sample contained 5.7% water as determined by Kari Fisoher titration. a
Compounds that contain active hydrogen atoms as well as alkyl halides, esters, epoxides, and azoxy compounds will consume hydride. If such compounds are present in quantity, enough hydride must be present in the reaction mixture to convert all the amide to amine. It is impossible to run dilute aqueous solutions of amides by this method, as too large an excess of reagent would be needed. However, samples containing 10% water were successfully run by this method. Samples containing 50% water showed results which were 10% low in amide, but using more hydride reagent may make it possible to run 50% aqueous solutions. It may be possible to run samples containing 25% water, but this was not tried. The precision of the analysis described below is usually within *2% and very often within & l %for the various amides tried. The accuracy is about the same as the precision; however, in many of the amides tried the precision of the nitrogen analysis (Dumas) used to assay the amides is poorer than the precision of the reduction method being tested. For the amides of nitrogen content below lo%, the accuracy values are controlled not by the reduction method but by the nitrogen method (the Dumas nitrogen analyses are reproducible to 3 ~ 0 . 2 %of nitrogen). The analysis is very simple to carry out and the apparatus is, for the most part, standard laboratory equipment. Precautions are required in handling lithium aluminum hydride; these are described on every package of the material. It is well not to use a hydride sample that is too old or that has been stored in a loosely stoppered container; it may be too hydrolyzed to be effective. REAGENTS
99.9
dV-laurovlsarcosine
ii Figure 1. Distillation apparatus
Lithium aluminum hydride. Ten g r a m of lithium aluminum hydride are refluxed with 500 ml. of anhydrous diethyl ether for several hours. If the hydride is finely divided, it will dissolve in a relatively short time. Insoluble products, formed by the reaction of impurities in the ether with the lithium aluminum hydride, settle on cooling, and the clear solution can be pipetted off as needed. The solution should be protected from atmospheric moisture. The usable life of the solution is about one month. Standard 0.02N sulfuric acid. Standard 0.02N sodium hydroxide. 6 N sodium hydroxide. Methyl purple indicator (Fleisher methyl purple, Burrell Corp., Pittsburgh, Pa.). Ethylene glycol. Isopropyl alcohol. DISTILLATION APPARATUS
The distilling apparatus used in Procedure A is the standard Kjeldahl steam distillation equipment. The distilling apparatus in Procedure B consists of a 200-ml.
ANALYTICAL CHEMISTRY
552 Table 11. Nitrile Results Compound Benzonitrile Butyronitrile N-capronitrile y-Chlorobenzonitrile
%
% by N
Procedure
98.90 98.69 98.81 96.15
98.67
.I
98.86
A
99.65
A
102.06
A
qfi - . 4n ._
96.72 98.45 99.07 97.76 99.95 98.93 99.76
refluxed on a steam bath for 0.5 hour. The flask is cooled to room temperature and the excess reagent is decomposed by dropwise addition of water. Sfter the reagent is completely decomposed, the sides of the flask are xashed with about 10 ml. of water, and 5 ml. of GN sodium hydroxide are added. A few boiling chips and 25 ml. of ethylene glycol are added before the flask is attached to the distilling apparatus. The solution is distilled a t a rapid rate nearly to dryness and 25 ml. of ethylene glycol are added through the stopcock on the connector at such a rate that boiling does not stop. The addition and distillation of 25-ml. portions of ethylene glycol are continued until 100 ml. have been distilled. The condenser is washed with approximately 50 ml. of hot isopropyl alcohol, and the amine contained in the distillate and washings is titrated potentiometrically with 0.02.V sulfuric acid. Per cent amide is calculated in the following manner:
round-bottomed flask connected to a Kjeldahl bulb which is attached to a water condenser by a 7 5 " connector. A stopcock and funnel are sealed on the connector a t the bend so that ethylene glycol can be dropped into the flask (see Figure 1). PROCEDURE A
.4n exactly weighed sample containing approximately 0.0006 mole of amide is placed in a 100-ml. Kjeldahl flask, and 5 ml. of lithium aluminum hydride reagent are added. The solution is allowed t o stand for 15 minutes at room temperature to ensure complete reduction of the amide, and the flask is then attached to the Kjeldahl distillation apparatus. A 200-ml. Erlenmeyer flask containing exactly 50 ml of 0.02.V sulfuric acid is placed on the apparatus, so that the end of the condenser is below the surface of the acid. Water is added dropwise to the reaction flask until the excess lithium aluminum hydride is decomposed. Ten milliliters of G N sodium hydroxide are added and steam distillation is carried out as in a Kjeldahl determination. About 50 ml. of distillate are collected in the 0.02N sulfuric acid and the excess acid is titrated with standard 0.02AVsodium hydroxide to the green end point of methyl purple indicator. Per cent amide is calculated as follows: (Titration for 50 ml. of acid - titration for sample) X W of S a O H X h'I.\T'. amide X 100 Weight of sample X 1000
=
% amide
ml. of H2S04 X N of H2SO4 X M.W. X 100 weight of sample X 1000 ACKYOWLEDGMENT
The authors would like to acknowledge the contribution of Thomas Bonstein, who ran the nitrogen analyses on the samples used in this study. LITERATURE CITED
Baerts, F., and Devlaux, P., Chimie & Industrie, Special S o . 743 (March 1931). Bergmann, F., AKAL.CHEM.,24, 1367 (1952). Dubnoff, J. W., J . Bid. Chem., 131, 163 (1939). Emmert, E. h l . , Plant Physiol., 14, 341 (1939). Hirai, M., and Hayatsu, R., J . Pharm. Soc. Japan, 71, 765 (1951); Hochstein, F. il., J . Am. Chem. Soc., 71, 305 (1949). Krynitsky, J. -4., Johnson, J. E., and Carhart, H. W., Ibid., 70, 486 (1948). Mitchell, J., and dshby, C. E., Ibid., 67, 161 (1945). Nystrom, R. F., and Brown, W. G., Ibid., 70, 3738 (1948). Olleman, E. D., r l x a ~CHEM.. . 24, 1425 (1952). Olsen, S.,Die Chemie, 56, 202 (1943). Renard, hl., and MCdart, J., Bull. SOC. r o y . sci. Lie'ge, 18, 409 (1949). Schrool, S . ,Pharni. Weekblad, 78, 433 (1941). Schryver, S.B., and Thomas, E. lI.,J . Inst. Brewing, 35, 571 (1929), VondrBk, J., Chimie & Industrie, Special No. 637 (May 1927). Zaugg, H. E., and Horrom, B. W., ANAL. CHEM.,20, 1026 (1948).
% amide
PROCEDUREB
A weighed sample containing approximately 0.0006 mole of amide is placed in a 200-ml. round-bottomed flask, and 10 ml. of lithium aluminum hydride reagent are added. The mixture is
=
RECEIVEDfor review October 22, 1954. 4ccepted December 18, 1954.
Polarographic Determination of Traces of Fluoride and Iron CARLYLE E. SHOEMAKER' M o u n d Laboratory, Monsanto Chemical Co., Miamisburg, O h i o
A method of analysis was required for microgram quantities of fluoride and iron in the presence of radioactive substances. Active oxygen and peroxides are formed in aqueous solutions as a result of intense radioactivity. These active substances attack dye and fluorescent salts used in many analytical methods for fluoride. A polarographic method, using rotating platinum microelectrodes, was developed in which the fluoride ion forms a complex with ferric iron and the ironfluoride complex is reduced irreversibly at potentials more negative than the reduction of ferric iron. The dissociation constant of FeF++ was determined and The method is suitable for found to be 6.9 X determination of microgram quantities of fluoride and iron in solutions containing radioactive substances. One microgram of fluoride and 0.33 microgram of iron may be determined with an accuracy of about 15%.
B
ECAUSE there n ere few satisfactory methods available, an analytical procedure for the determination of microgram amounts of fluoride and iron in the presence of high-level radioactivity has been developed. Many of the microgram analytical methods reported for determination of fluoride depend on a bleaching action of fluoride on a colored or fluorescent metalorganic salt (15, 2 2 ) . These methods are not accurate because of insensitivity of the end point, but some improvement in them has been made bv using a spectrophotometer (6) or fluorometer (17, 2 3 ) to determine the end point. Other amperometric titrations for fluoride could not be used on a microgram scale because of limitations of solubility or interferences ( 3 , $, 16, 2 0 ) . Active oxygen and peroxides are formed in aqueous solutions as a result of intense radioactivity (8). This active oxygen attacks the dye in colorimetric methods for fluoride analysis, caus1
Present address, J. T. Baker Chemical Co., Phillipsburg, N. J.
