Microscopic crystal tests
Group B. - Reserpine and related alkaloids
Group C. - The diphenylmethane derivatives
Group D. - The substituted butanediols, propandiols, dioxalanes, and related compounds
Group E. - The ureides, amides, hydrazines and related compounds
Group F. - Miscellaneous compounds
Author: Ponnusamy Rajeswaran, Paul L. Kirk
Pages: 21 to 32
Creation Date: 1961/01/01
Note by the editor: This part of the article is a continuation of part I, which was included in Volume XIII, No. 3, of the Bulletin.
Crystal examination under the microscope is a rapid means of differentiating chemical compounds, and therefore a significant step in their identification. It requires small quantities of material, and utilizes relatively simple operations. The tendency to substitute for crystal tests such instrumental methods as spectrophotometry and vapour-phase chromatography does not diminish the value of the microscopic procedures for preliminary studies, which often lead to positive identification with minimum effort.
Starting with the historical work of Orfila [ (1)] , a pioneer in forensic toxicology, practically every common and many uncommon compounds, both organic and inorganic, have been identified by this approach. When performed by such techniques as that of Clarke [ (2)] , crystal tests provide not only ease of operation, but great reliability in their interpretation.
Fusion, sublimation and recrystallization tests from alcoholic and ammoniacal solutions were performed on 48 of the compounds listed in this study. Two or three of them have been reported previously [ (3)] . Most of the compounds were obtained in the pure crystal form, and extraction procedures were used to isolate seven of them from available prescription form.
Sublimation was performed by placing a few milligrammes of the compound in a depression of a cavity slide with a cover glass. The slide, placed on a melting point block, was heated gradually to a temperature of 250°C. Melting points were not determined.
11 This work was supported by grants from the National Institutes of Health, Public Health Service, Department of Health, Education and Welfare (RG-4372), and the Research Committee of the University of California. Acknowledgement is made to thirty manufacturers of tranqnillizing drugs for supplying samples of their products.
Fusion was performed by heaping a bit of the compound on the corner of a glass slide and covering with a cover slip, after which the material was warmed by moving it slowly into the flame of a microburner. The temperature was increased until melting commenced, the slide being held in this position for a short while before being removed from the flame, to avoid overheating and decomposition. After cooling, the melt showed the presence of crystals in some instances, where the temperature gradient was established. In other instances there were variations of the form of the solidified melt.
Recrystallization from alcoholic solutions was performed with milligramme amounts of the compound to which were added, on a slide, a drop of 50% aqueous alcohol acidified with 6N hydrochloric acid. The compound was dissolved by stirring with a glass rod, warming over a microburner flame when necessary. The preparation was covered with a cover glass and allowed to cool and evaporate at room temperature. The solvent was not found suitable for some compounds, especially phenothiazine derivatives, for which 95% alcohol was used instead.
Recrystallization from ammoniacal solutions was obtained from concentrated ammonia solutions made similarly to the above description. In some instances a 50% alcoholic ammonia solution was used. Phenothiazine derivatives formed emulsions with ammoniacal solution, as also did the Rauwolfia group of alkaloids.
All preparations were photographed at 75X or 150X as indicated, and are shown in plates 1 to 6.
Compound |
I Sublimation |
II Fusion |
III Re-crystallization from 50% alcohol : HCl |
|
---|---|---|---|---|
Magnification
|
||||
Plate 1 a Row 1
|
Promazine
|
150 x | 75 x |
150 x (95% alcohol)
|
2 |
Promethazine
|
150 x | 75 x |
75 x; 75 x (95% alcohol)
|
3 |
Ethopropazine
|
150 x |
-
|
150 x |
4 |
Trimeperazine
|
-
|
75 x | 150 x |
Plate 1 b Row 1
|
Pyrathiazine
|
150 x |
-
|
150 x (95% alcohol)
|
2 |
Chlorpromazine
|
150 x | 75 x |
75 x (95% alcohol)
|
3 |
Prochlorperazine
|
150 x | 75 x | 150 x |
4 |
Prochlorperazine-ethane disulfonate
|
-
|
75 x | 150 x |
Plate 1 c Row 1
|
Prochlorperazine-dimaleate
|
150 x | 75 x | 150 x |
2 |
Perphenazine
|
-
|
75 x |
75 x (95% alcohol)
|
3 |
Thiopropazate
|
-
|
75 x |
150 x (95% alcohol)
|
4 |
Triflupromazine
|
150 x | 75 x |
75 x (95% alcohol)
|
Plate 1 d Row 1
|
Trifluoperazine
|
150 x |
-
|
150 x (95% alcohol)
|
2 |
Fluphenazine
|
-
|
75 x |
75 x (95% alcohol)
|
3 |
Methoxypromazine
|
-
|
75 x |
75 x (95% alcohol)
|
4 |
Mepazine
|
150 x | 75 x | 75 x |
Compound |
II Fusion |
III Re-crystallization from 50 % alcohol: HCl |
|
---|---|---|---|
Magnification
|
Magnification
|
||
Row 1
|
Reserpine
|
75 x | 75 x |
2 |
Deserpidine
|
75 x | 75 x |
3 |
Rescinnamine
|
75 x | 150 x |
4 |
Alseroxylon
|
75 x | 150 x |
Compound |
I Sublimation |
II Fusion |
III Re-crystallization from 50% alcohol: HCl |
IV Re-crystallization from conc. ammonia |
|
---|---|---|---|---|---|
Magnification
|
|||||
Plate 3
a Row 1
|
Adiphenine
|
-
|
75 x |
75 x (95% alcohol)
|
150 x |
2 |
Diphenylpyraline
|
150 x | 75 x | 75 x | 150 x |
3 |
Azacylonol
|
150 x | 75 x | 75 x | 75 x |
Plate 3
b Row 1
|
Captodiamine
|
-
|
75 x | 150 x |
-
|
2 |
Chlorcylyzine
|
75 x;75 x
|
75 x |
75 x (95% alcohol)
|
-
|
3 |
Benactyzine
|
150 x |
-
|
150 x |
-
|
4 |
Pipradol
|
150 x | 75 x | 75 x |
-
|
Plate 3
c Row 1
|
Hydroxyzine
|
150 x |
-
|
75 x (95% alcohol)
|
-
|
2 |
Meclizine
|
150 x | 75 x | 75 x |
-
|
3 |
Buclizine
|
150 x |
-
|
75 x |
-
|
Compound |
I Sublimation |
II Fusion |
III Re-crystallization from 50 % alcohol; HCl |
IV Re-crystallization from conc. ammonia |
|
---|---|---|---|---|---|
Magnification
|
|||||
Row 1
|
Phenaglycadol
|
150 x | 75 x | 150 x | 75 x |
2 |
Mephenesin
|
75 x | 75 x |
75 x (95% alcohol)
|
75 x |
3 |
Meprobamate
|
-
|
75 x | 75 x | 75 x |
Compound |
I Sublimation |
II Fusion |
III Re-crystallization from 50 % alcohol; HCl |
IV Re-crystallization from conc. ammonia |
|
---|---|---|---|---|---|
Magnification
|
|||||
Plate 5
a Row 1
|
Phenelzine
|
-
|
75 x |
75 x (95% alcohol)
|
150 x |
2 |
a-methyl-phenethyl-hydrazine
|
-
|
75 x |
75 x (95% alcohol)
|
150 x |
3 |
Isocarboxazide
|
150 x | 75 x | 150 x |
75 x (50% alcohol: ammonia)
|
Plate 5
b Row 1
|
Iproniazid
|
-
|
75 x | 150 x |
75 x (50% alcohol: ammonia)
|
2 |
Nialamide
|
-
|
75 x | 75 x |
75 x (50% alcohol: ammonia)
|
3 |
Ectylurea
|
150 x | 75 x | 75 x | 75 x |
Plate 5
c Row 1
|
Oxonamide
|
150 x | 75 x | 75 x | 75 x |
2 |
Acetylcarbromal
|
150 x | 75 x | 150 x | 75 x |
3 |
Glutethimide
|
150 x | 75 x | 75 x | 150 x |
Compound |
I Sublimation |
II Fusion |
III Re-crystallization from 50 % alcohol; HCl |
IV Re-crystallization from conc. ammonia |
|
---|---|---|---|---|---|
Magnification
|
|||||
Plate 6
a Row 1
|
Methylphenidate
|
150 x | 75 x | 150 x |
150 x (50% alcohol: ammonia)
|
2 |
Thonzylamine
|
150 x | 75 x |
75 x (95% alcohol)
|
150 |
3 |
Pyrrobutamine
|
-
|
75 x | 150 x | 75 x |
Plate 6
b Row 1
|
Chlormethazanone
|
-
|
-
|
150 x | 150 x |
2 |
Imipramine
|
150 | 75 x |
75 x (95% alcohol)
|
75 x |
3 |
3-(β-aminoethyl) pyrazole
|
-
|
75 x |
150 x (95% alcohol)
|
150 x |
ORFILA, M. P., A General System of Toxicology , Cox, London. 1821.
002CLARKE, E. G. C., Bull. Narcotics, U.N. XI (1), 27; 1959.
003PENPRASE, W. G. & BILES, J. A., Am. Pharm. Assoc ., Sci. Ed. XLV (9). 585; 1956. J. Am. Pharm. Assoc., Sci. Ed. VLVII (7), 523; 1958.