Tranquillizing and related drugs: Properties for their identification (part II)

Sections

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

Details

Author: Ponnusamy Rajeswaran, Paul L. Kirk
Pages: 21 to 32
Creation Date: 1961/01/01

Tranquillizing and related drugs: Properties for their identification (part II)

Ponnusamy Rajeswaran School of Criminology
Paul L. Kirk 1 University of California, Berkeley

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.

Microscopic crystal tests

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.

1

1 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.

PLATES 1 a , 1 b , 1 c , 1 d

 

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

PLATE 1 a

Full size image: 175 kB, PLATE 1 a

PLATE 1 b

Full size image: 163 kB, PLATE 1 b

PLATE 1 c

Full size image: 175 kB, PLATE 1 c

PLATE 1 d

Full size image: 167 kB, PLATE 1 d

Group B. - Reserpine and related alkaloids

 

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
Full size image: 150 kB

Group C. - The diphenylmethane derivatives

PLATES 3 a , 3 b , 3 c

 

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
-

PLATE 3 a

Full size image: 201 kB, PLATE 3 a

PLATE 3 b

Full size image: 196 kB, PLATE 3 b

PLATE 3 c

Full size image: 123 kB, PLATE 3 c

Group D. - The substituted butanediols, propandiols, dioxalanes, and related compounds

PLATE 4

 

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

Full size image: 189 kB

Group E. - The ureides, amides, hydrazines and related compounds

PLATES 5 a 5 b 5 c

 

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

PLATE 5 a

Full size image: 201 kB, PLATE 5 a

PLATE 5 b

Full size image: 298 kB, PLATE 5 b

PLATE 5 c

Full size image: 171 kB, PLATE 5 c

Group F. - Miscellaneous compounds

PLATES 6 a , 6 b

 

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

PLATE 6 a

Full size image: 123 kB, PLATE 6 a

PLATE 6 b

Full size image: 123 kB, PLATE 6 b

REFERENCES

001

ORFILA, M. P., A General System of Toxicology , Cox, London. 1821.

002

CLARKE, E. G. C., Bull. Narcotics, U.N. XI (1), 27; 1959.

003

PENPRASE, W. G. & BILES, J. A., Am. Pharm. Assoc ., Sci. Ed. XLV (9). 585; 1956. J. Am. Pharm. Assoc., Sci. Ed. VLVII (7), 523; 1958.