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Note on the microdetermination of chlorine in organic compounds
MICROCHEMICAL
Note
JOURNAL
8,329.333(1964)
on the Microdetermination Organic
AL STEYERMARK,
RUTH
Hogmann-La
of Chlorine
Compounds
R. KAUP, AND BOHDANNA Roche Inc., Nutley,
Received
in
BLAZENKO
Xew Jersey
August 6, 196-I
INTRODUCTION
The purpose of this paper is to alert the microanalyst to the possibility of his unknowingly reporting incorrect results, regardless of the method employed for a determination. The purpose is certainly not to discredit the reliable Carius method. The importance of using more than one method for certain microdeterminations (particularly those of halogens, sulfur, nitrogen, and molecular weight) has already been stressed by one of us (13). To a certain extent, this is also recognized by the fact that lists of recommended test substances have been published to prove the applicability of apparatus and method for various determinations when dealing with different combinations of elements and types of structures (3-6). To illustrate the above, the results obtained in this laboratory on two chloro compounds, I and II, warrant their being called to the attention of the microanalyst. Structure types are involved in both cases, and although it is not yet understood just how, the combination of types might contribute to the difficulties of analysis. It should be noted that the results
COMPOUND
isoquinoline
I: dl-l-(4-chlorophenethyl)-1,2,3,4-tetrahydro-6,7-dimethox~-2-methyl(C,,H,,O,NCI) .
reported here are the only ones obtained on these compounds; they are not “selected” values. 329
330
AL
STEYERMARK
ET
AL.
Research compound II has marked points of similarity to compound I. It contains the same elements, and it too has only one chlorine atom, which is nonionic and attached to an aromatic nucleus. Both compounds I and II have two methoxyl groups attached to an aromatic nucleus, and both contain only one nitrogen atom; this is in the form of a tertiary amine to which is attached a methyl group. The three methods of analysis referred to below were used. For the determination of bromine, chlorine, and iodine, the gravimetric Carius method (8, 13) has been the choice method in our laboratory for the past 24 years. The gravimetric Pregl catalytic combustion method (13) and the Schijniger combustion procedure followed by potentiometric titration (9) have been used on occasion for referee purposes. All three methods have been proved to be reliable. The Carius one was adopted as the official method for the Association of Official Agricultural Chemists after they conducted an exhaustive collaborative study (8, 13-18) in which the Pregl procedure gave almost as good results (13, 17, 18). The TABLE
1
RESULTS OBTAINED 0~ SAMPLE 0~ dl-1-(4-CHLOR~PHENETHYL)-1,2,3,4-TETRAIIYDRO-6,7-DIMETHOXY-2-METHYLISOQUINOLINE Elemenk or group
C
Calculated
69.45
(% )
Found
(%)
69.78, 69.41
H
6.99
6.84, 7.10
N 0
4 .Oj 9.25
4.10 9.48, 8.97
Cl
10.25
7.90, 7.81, 7.91,7.48, 7.55, 7.47, 8.52, 9.38 (Carius) 10.41, 10.56, 10.24 (Pregl) 10.13, 10.16, 9.91 (SchSniger)
CH,O
17.9s
18.32, 18.27
Schijniger oxygen flask combustion method for the determination of bromine, chlorine, and iodine has become so popular among analysts (1, 2, 7, 9-12, 19) that it was subjected to collaborative study this year by the above-mentioned Association. The results reported by the thirty collaborators were so good (16) that, as of this writing, it would appear that some modification of it will eventually be adopted as an official method of that Association. Table 1 shows the theoretical and found values for compound I. There
MICRODETERMINATION
331
OF CHLORINE
is good agreement between the theoretical and found values for carbon, hydrogen, nitrogen, oxygen, and methoxyl, and no difficulties were experienced with these determinations. However, the chlorine values found by the Carius method are very low? and six of the eight values are in close agreement with one another (the difference between these being only 0.44% between the highest and the lowest, i.e., 7.47-7.91s). The best of the Carius values was 0.8770 low. Increasing the time and temperature of combustion up to 10 hours and 3OO”C, respectively, did not improve the results. On the other hand, the values obtained by the Pregl catalytic combustion are all in good agreement with the theoretical values, and there were no difficulties with the determination. Likewise, the values obtained by the Schijniger combustion (followed by the potentiometric titration with silver nitrate by usin,u silver-silver chloride versus silver electrodes) were in good agreement with the theoretical values, although they were on the low side. Obviously. all three methods were checked at TABLE RESULTS
Element or group
OBTAISED
ON SAMPLE
2 OF RESEARCII
Calculated (“/o)
COMPOUND
II
Found (%, 67.89, 68.12
C
67.60
H h-
6.93
6.85, 6.90
4.38
4.13, 4.26
0
10.00
10.11, 10.36
Cl
11.09
9.97, 10.16 (Carius) 10.97.11.03 (Pregl)
CH,O
19.41
19.37
the time of the determinations on compounds I and II by using a test substance ($+chloroacetanilide) . They also gave good results with other research compounds. Table 2 shows the results obtained on research compound II. Again. low results were obtained by the Carius method, and correct values were obtained by the Pregl catalytic combustion. The found values for carbon, hydrogen, nitrogen, oxygen, and methoxyl are in good agreement with the theoretical ones. SUMMARY The importance of using more than one method of analysis is shown by the results obtained on two compounds, both of which have structural points of aimi-
332
AL
STEYERMARK
ET AL.
larity. Chlorine values obtained by the gravimetric Carius method were low, but those obtained by the gravimetric Pregl catalytic combustion and the Schoniger combustion methods were in agreement with the theoretical values. ACKNOWLEDGMENTS The authors are indebted to Esther A. Bass and Barbara the analyses other than those of the chlorine.
E. McGee
for some of
REFERENCES 1. 2.
F. W., A rapid method for microdetermination of halogen in organic compounds. Micvochem. J. 8, 537-542 (1959). CHILDS, C. E., MEYERS, E. E., CHENG, J., LAFRAMBOISE, E., AND BALODIS, R. B., A study of the oxygen flask combustion procedure. Microchem. J. 7, 266-271
CHENG,
(1963). 3.
4.
5.
COMMISSION ON MICROCHEMICAL TECHNIQUES, SECTION OF ANALYTICAL CHEMISTRY, INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY, Recommended test substances for the microdetermination of carbon and hydrogen. Pure Appl. Chem. 1, 143-145 (1960). COMMISSION ON MICROCHEMICAL TECHNIQUES, SECTION OF ANALYTICAL CHEMISTRY, INTERNATIONAL UNION 01: PURE AND APPLIED CHEMISTRY, Recommended test substances for the microdetermination of nitrogen in organic compounds. Pure Appl. Chem. 3, 513-515 (1961). COMMISSION ON MICROCHEMICAL ISTRY, INTERNATIONAL UNION
TECHNIQUES, SECTION OF ANALYTICAL OF PURE AND APPLIED CHEMISTRY,
mended test substances for the microdetermination of halogens in organic compounds. Pure Appl. Chem. 5, 759-761 (1962). 6.
COMMISSION ON MICROCHEMICAL ISTRY, INTERNATIONAL UNION
CHEM-
Recomand sulfur
TECHNIQUES, DIVISION OF ANALYTICAL CHEMISTRY, OF PURE AND APPLIED
CHEM-
Recomof oxygen in organic com-
mended test substances for the microdetermination pounds. Pure Appl. Chew. 7, 707-709 (1963). 7. FILDES, J. E., AND MACDONALD, A. M. G., Titrimetric methods of halogens in organic compounds by the rapid combustion procedure. I. The determination of the individual halogens. Anal. Chim. Acta 24, 121-127 (1961). 8. HORWITZ, W. (EDITOR), “Official Methods of the Association of Official Agricultural Chemists,” 9th edition, pp. 640-641. Association of Official Agricultural Chemists, Washington, D.C., 1960. 9. INGRAM, G., “Methods of Organic Elemental Microanalysis,” 511 pp. Reinhold, New York, 1962. 10. SCH~NIGER, W., Die Kolbenmethode in der organischen Mikroelementaranalyse. 2. anal. Chem. 181, 28-39 (1960). 11. SCH~NIGER, W., Die mikroanalytische Schnellbestimmung von Halogenen und Schwefel in organischen Verbindungen. Mikrochem. Acta 1956, 869-876. 12. SCH~NIGER, W., Eine mikroanalytische Schnellbestimmung von Halogen in organischen Substanzen. Mikrochim. Acta 1955, 123-129. 13. STEYERMARK, AL, “Q uan t i t a t’rve Organic Microanalysis,” 2d edition, 665 pp. Academic Press, New York, 1961.
MICRODETERMINATION
14.
STEYERMARK, .4~, Report
on microanalytical
333
OF CHLORINE
determination
of iodine.
determination
of iodine:
J. Assoc.
Ofic. Agr. Chemists 40, 381-386 (1957). 15.
STEYERMARX, AL, Report
on microanalytical
Part
II.
J. Assoc. Ofic. Agr. Chemists 41, 297-299 (1958). 16.
17.
18. 29.
STEYERMARK, AL, Report on microanalytical determination of bromine, chlorine, and iodine employing oxygen flask combustion. J. Assoc. Ofic. Agr. Chemists 48, in press (1965). STEYERMARK, AL, AND FAULKNER, M. B., Report on microanalytical determinations of bromine and chlorine. J. Assoc. Ofic. Agr. Chemists 35, 291-304 (1952). STEYERMARK, ,4~, IIND GARNER, M. W., Report on microanalytical determinations of bromine and chlorine. J. Assoc. Ofic. iigr. Chemists 36, 319-335 (1953). WHITE, D. C., Microdetermination of chlorine or bromine in organic compounds. Mikrochim. Acta 1961, 449-456.
Note
JOURNAL
8,329.333(1964)
on the Microdetermination Organic
AL STEYERMARK,
RUTH
Hogmann-La
of Chlorine
Compounds
R. KAUP, AND BOHDANNA Roche Inc., Nutley,
Received
in
BLAZENKO
Xew Jersey
August 6, 196-I
INTRODUCTION
The purpose of this paper is to alert the microanalyst to the possibility of his unknowingly reporting incorrect results, regardless of the method employed for a determination. The purpose is certainly not to discredit the reliable Carius method. The importance of using more than one method for certain microdeterminations (particularly those of halogens, sulfur, nitrogen, and molecular weight) has already been stressed by one of us (13). To a certain extent, this is also recognized by the fact that lists of recommended test substances have been published to prove the applicability of apparatus and method for various determinations when dealing with different combinations of elements and types of structures (3-6). To illustrate the above, the results obtained in this laboratory on two chloro compounds, I and II, warrant their being called to the attention of the microanalyst. Structure types are involved in both cases, and although it is not yet understood just how, the combination of types might contribute to the difficulties of analysis. It should be noted that the results
COMPOUND
isoquinoline
I: dl-l-(4-chlorophenethyl)-1,2,3,4-tetrahydro-6,7-dimethox~-2-methyl(C,,H,,O,NCI) .
reported here are the only ones obtained on these compounds; they are not “selected” values. 329
330
AL
STEYERMARK
ET
AL.
Research compound II has marked points of similarity to compound I. It contains the same elements, and it too has only one chlorine atom, which is nonionic and attached to an aromatic nucleus. Both compounds I and II have two methoxyl groups attached to an aromatic nucleus, and both contain only one nitrogen atom; this is in the form of a tertiary amine to which is attached a methyl group. The three methods of analysis referred to below were used. For the determination of bromine, chlorine, and iodine, the gravimetric Carius method (8, 13) has been the choice method in our laboratory for the past 24 years. The gravimetric Pregl catalytic combustion method (13) and the Schijniger combustion procedure followed by potentiometric titration (9) have been used on occasion for referee purposes. All three methods have been proved to be reliable. The Carius one was adopted as the official method for the Association of Official Agricultural Chemists after they conducted an exhaustive collaborative study (8, 13-18) in which the Pregl procedure gave almost as good results (13, 17, 18). The TABLE
1
RESULTS OBTAINED 0~ SAMPLE 0~ dl-1-(4-CHLOR~PHENETHYL)-1,2,3,4-TETRAIIYDRO-6,7-DIMETHOXY-2-METHYLISOQUINOLINE Elemenk or group
C
Calculated
69.45
(% )
Found
(%)
69.78, 69.41
H
6.99
6.84, 7.10
N 0
4 .Oj 9.25
4.10 9.48, 8.97
Cl
10.25
7.90, 7.81, 7.91,7.48, 7.55, 7.47, 8.52, 9.38 (Carius) 10.41, 10.56, 10.24 (Pregl) 10.13, 10.16, 9.91 (SchSniger)
CH,O
17.9s
18.32, 18.27
Schijniger oxygen flask combustion method for the determination of bromine, chlorine, and iodine has become so popular among analysts (1, 2, 7, 9-12, 19) that it was subjected to collaborative study this year by the above-mentioned Association. The results reported by the thirty collaborators were so good (16) that, as of this writing, it would appear that some modification of it will eventually be adopted as an official method of that Association. Table 1 shows the theoretical and found values for compound I. There
MICRODETERMINATION
331
OF CHLORINE
is good agreement between the theoretical and found values for carbon, hydrogen, nitrogen, oxygen, and methoxyl, and no difficulties were experienced with these determinations. However, the chlorine values found by the Carius method are very low? and six of the eight values are in close agreement with one another (the difference between these being only 0.44% between the highest and the lowest, i.e., 7.47-7.91s). The best of the Carius values was 0.8770 low. Increasing the time and temperature of combustion up to 10 hours and 3OO”C, respectively, did not improve the results. On the other hand, the values obtained by the Pregl catalytic combustion are all in good agreement with the theoretical values, and there were no difficulties with the determination. Likewise, the values obtained by the Schijniger combustion (followed by the potentiometric titration with silver nitrate by usin,u silver-silver chloride versus silver electrodes) were in good agreement with the theoretical values, although they were on the low side. Obviously. all three methods were checked at TABLE RESULTS
Element or group
OBTAISED
ON SAMPLE
2 OF RESEARCII
Calculated (“/o)
COMPOUND
II
Found (%, 67.89, 68.12
C
67.60
H h-
6.93
6.85, 6.90
4.38
4.13, 4.26
0
10.00
10.11, 10.36
Cl
11.09
9.97, 10.16 (Carius) 10.97.11.03 (Pregl)
CH,O
19.41
19.37
the time of the determinations on compounds I and II by using a test substance ($+chloroacetanilide) . They also gave good results with other research compounds. Table 2 shows the results obtained on research compound II. Again. low results were obtained by the Carius method, and correct values were obtained by the Pregl catalytic combustion. The found values for carbon, hydrogen, nitrogen, oxygen, and methoxyl are in good agreement with the theoretical ones. SUMMARY The importance of using more than one method of analysis is shown by the results obtained on two compounds, both of which have structural points of aimi-
332
AL
STEYERMARK
ET AL.
larity. Chlorine values obtained by the gravimetric Carius method were low, but those obtained by the gravimetric Pregl catalytic combustion and the Schoniger combustion methods were in agreement with the theoretical values. ACKNOWLEDGMENTS The authors are indebted to Esther A. Bass and Barbara the analyses other than those of the chlorine.
E. McGee
for some of
REFERENCES 1. 2.
F. W., A rapid method for microdetermination of halogen in organic compounds. Micvochem. J. 8, 537-542 (1959). CHILDS, C. E., MEYERS, E. E., CHENG, J., LAFRAMBOISE, E., AND BALODIS, R. B., A study of the oxygen flask combustion procedure. Microchem. J. 7, 266-271
CHENG,
(1963). 3.
4.
5.
COMMISSION ON MICROCHEMICAL TECHNIQUES, SECTION OF ANALYTICAL CHEMISTRY, INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY, Recommended test substances for the microdetermination of carbon and hydrogen. Pure Appl. Chem. 1, 143-145 (1960). COMMISSION ON MICROCHEMICAL TECHNIQUES, SECTION OF ANALYTICAL CHEMISTRY, INTERNATIONAL UNION 01: PURE AND APPLIED CHEMISTRY, Recommended test substances for the microdetermination of nitrogen in organic compounds. Pure Appl. Chem. 3, 513-515 (1961). COMMISSION ON MICROCHEMICAL ISTRY, INTERNATIONAL UNION
TECHNIQUES, SECTION OF ANALYTICAL OF PURE AND APPLIED CHEMISTRY,
mended test substances for the microdetermination of halogens in organic compounds. Pure Appl. Chem. 5, 759-761 (1962). 6.
COMMISSION ON MICROCHEMICAL ISTRY, INTERNATIONAL UNION
CHEM-
Recomand sulfur
TECHNIQUES, DIVISION OF ANALYTICAL CHEMISTRY, OF PURE AND APPLIED
CHEM-
Recomof oxygen in organic com-
mended test substances for the microdetermination pounds. Pure Appl. Chew. 7, 707-709 (1963). 7. FILDES, J. E., AND MACDONALD, A. M. G., Titrimetric methods of halogens in organic compounds by the rapid combustion procedure. I. The determination of the individual halogens. Anal. Chim. Acta 24, 121-127 (1961). 8. HORWITZ, W. (EDITOR), “Official Methods of the Association of Official Agricultural Chemists,” 9th edition, pp. 640-641. Association of Official Agricultural Chemists, Washington, D.C., 1960. 9. INGRAM, G., “Methods of Organic Elemental Microanalysis,” 511 pp. Reinhold, New York, 1962. 10. SCH~NIGER, W., Die Kolbenmethode in der organischen Mikroelementaranalyse. 2. anal. Chem. 181, 28-39 (1960). 11. SCH~NIGER, W., Die mikroanalytische Schnellbestimmung von Halogenen und Schwefel in organischen Verbindungen. Mikrochem. Acta 1956, 869-876. 12. SCH~NIGER, W., Eine mikroanalytische Schnellbestimmung von Halogen in organischen Substanzen. Mikrochim. Acta 1955, 123-129. 13. STEYERMARK, AL, “Q uan t i t a t’rve Organic Microanalysis,” 2d edition, 665 pp. Academic Press, New York, 1961.
MICRODETERMINATION
14.
STEYERMARK, .4~, Report
on microanalytical
333
OF CHLORINE
determination
of iodine.
determination
of iodine:
J. Assoc.
Ofic. Agr. Chemists 40, 381-386 (1957). 15.
STEYERMARX, AL, Report
on microanalytical
Part
II.
J. Assoc. Ofic. Agr. Chemists 41, 297-299 (1958). 16.
17.
18. 29.
STEYERMARK, AL, Report on microanalytical determination of bromine, chlorine, and iodine employing oxygen flask combustion. J. Assoc. Ofic. Agr. Chemists 48, in press (1965). STEYERMARK, AL, AND FAULKNER, M. B., Report on microanalytical determinations of bromine and chlorine. J. Assoc. Ofic. Agr. Chemists 35, 291-304 (1952). STEYERMARK, ,4~, IIND GARNER, M. W., Report on microanalytical determinations of bromine and chlorine. J. Assoc. Ofic. iigr. Chemists 36, 319-335 (1953). WHITE, D. C., Microdetermination of chlorine or bromine in organic compounds. Mikrochim. Acta 1961, 449-456.