Part IVB. Infrared Spectra of Narcotics and Related Alkaloids

Sections

VALUE OF CATALOGUE OF NARCOTICS SPECTRA
EXPERIMENTAL PROCEDURES
ACKNOWLEDGMENTS

Details

Author: Leo Levi, Charles E. Hubley, R. A. Hinge
Pages: 42 to 45
Creation Date: 1955/01/01

PHYSICAL METHODS FOR THE IDENTIFICATION OF NARCOTICS (Continued)

Part IVB. Infrared Spectra of Narcotics and Related Alkaloids

Leo Levi
Food and Drug Laboratories, Department of National Health and Welfare, Ottawa, Canada Charles E. Hubley
R. A. Hinge
Defence Research Chemical Laboratories, Defence Research Board, Ottawa, Canada

Within the last five years considerable efforts have been expended by a number of industrial and research laboratories to assemble the IR spectra of groups of chemical compounds for reference purposes and as a result of these survey projects several extensive collections of such data exist [1] . Unfortunately, none of these catalogues includes the narcotic drugs and closely related alkaloids and it is the purpose of this paper to present an atlas of such spectra.

VALUE OF CATALOGUE OF NARCOTICS SPECTRA

The spectra presented in this atlas were recorded as mineral oil mulls and, where possible, as chloroform solutions. They should prove of particular value to the forensic chemist concerned with the identification and characterization of addiction-producing drugs seized in the illegal traffic or isolated from biological materials, and they will also be of considerable interest to the organic chemist faced with problems of structure elucidation. Eighty-five compounds have been included in this survey, and a detailed interpretation of the experimental data in terms of group frequencies and other structural correlations will form the subject of a subsequent paper in this series.

EXPERIMENTAL PROCEDURES

Mineral Oil (Nujol) Spectra

These spectra were obtained by grinding finely with an electric vibrator a few mg. of sample in mineral oil, placing the resultant smooth paste between two salt plates and measuring its absorption throughout the 2-16 micron range. Although mineral oil was used in the reference cell its absorption bands (3.5, 6.9 and 7.3 micron) were not completely compensated. All of the spectra were charted on a Baird Double Beam Recording IR Spectrophotometer equipped with rock salt optics and housed in an air-conditioned laboratory thermostated at 25°C.

Chloroform Spectra

From a series of media tried chloroform was considered the most suitable one because of its superiority as both an infrared and general solvent. The spectra were taken of approximately 1.4 per cent solutions, a pair of 0.455 mm. matched sodium chloride cells being used throughout the experiments. In cells of such thickness, required because of solubility limitations, chloroform shows relatively intense bands at 3.3, 4.18, 6.48, 7.0, 8.2, 9.6, 10.78 and beyond 12 microns. Hence, in these regions the inherent spectral characteristics of the compounds are either distorted or obscured, and because of the complete masking of sample absorption beyond 12 microns the spectra are shown up to this wavelength only. It would, therefore, be very desirable to supplement this altas with IR spectra of these alkaloids dissolved in other solvents having complementary absorption regions [1] .

SCOPE OF COLLECTION

The compounds included in this survey are shown in table I, which also lists many of their common synonyms and trade names1 under which they are marketed. Their authentication was reported in a previous paper of this series [2] and additional comments regarding their physico-chemical properties have been made by Oestreicher et al. [3] , Barnes and Sheppard [4] , and Barnes and Forsyth [5] . Thirteen of the compounds listed were not included in any of the previous projects and the infrared absorption spectra recorded in this atlas are the first absorption data to be published respecting those alkaloids. Other physical properties of these drugs are given in table II.

With the exception of 2-azabicyclo- (3,3,1) nonane hydrochloride, which compound was kindly supplied by Professor M. W. Cronyn of the University of California, Berkeley, Cal., all of the alkaloids shown in this table were obtained from T. and H. Smith, Ltd., Edinburgh, Scotland.

1

Trade-marks registered in the United States Patent Office up to July-August 1951 are indicated in the alphabetical listing by the use of the symbol R enclosed in a circle.

ACKNOWLEDGMENTS

The authors are grateful to the Defence Research Board, Ottawa, for permission to determine the spectra in their laboratories, and to both the Food and Drug Directorate of the Department of National Health and Welfare, Ottawa, and the Defence Research Board, Ottawa, for permission to publish these data. They are also indebted to Miss M. Smith, a summer student at the Defence Research Chemical Laboratories, and Mrs. P. O. Oestreicher of the Food and Drug Laboratories, Department of National Health and Welfare, for valuable technical assistance, and to Mr. C. A. Kerr, Chief Photographer of the Department of National Health and Welfare, for preparation of the illustrative material.

[Manuscripts Parts IVA and IVB received for review 1st December 1954]

Table I

ATLAS or IR-SPECTRA OF NARCOTICS AND RELATED ALKALOIDS

Spectrum number

Compound

Mineral oil Mull

Chloroform

Acedicon® Hydrochloride
81 36
dl- a-Acetylmethadol Hydrochloride
23 14
dl-Amidone
19 13
dl-Amidone Hydrochloride
20 37
Apomorphine Hydrochloride
41 -
Apomorphine Sulfate
42 -
2-Azabicyclo-(3,3,1)-nonane Hydrochloride
45 24
Bemidone
10 -
Bemidone Hydrochloride
11 -
Cliradon®
14 -
Cliradon® Hydrochloride
15 -
Cocaine
3 2
Cocaine Hydrochloride
4 -
Codeine
60 27
Codeine Hydrobromide
61 -
Codeine Hydrochloride
62 -
Codeine Hydrogen Iodide
63 -
Codeine Phosphate
64 -
Codeine Sulfate
65 -
Codeine, dihydro
70 28
Codeinone, dihydro
72 31
Codeinone, dihydro, Bitartrate
73 -
Codeinone, dihydro, Enol Acetate Hydrochloride
81 36
Codeinone, dihydrohydroxy, Hydrochloride
75 32
Cotarnine
28 18
Cotarnine Chloride
29 19
Cotarnine Phthalate
30 -
Cryptopine
39 22
Demerol®
5 4
Demerol® Hydrochloride
6 -
Diamorphine
79 35
Diamorphine Hydrochloride
80 -
Dicodid®
72 31
Dicodid® Bitartrate
73 -
Dilaudid® Hydrochloride
71 -
Dionin Hydrochloride
76 -
Dioxyline Phosphate
38 -
Dolantin
5 4
Dolantin Hydrochloride
6 -
Dolophine®
19 13
Dolophine® Hydrochloride
20 37
Dromoran®
46 -
Dromoran® Hydrobromide
47 -
l-Dromoran® Tartrate
48 -
Ecgonine
- 3
Ecgonine, benzoyl methyl
3 2
Ecgonine, benzoyl methyl, Hydrochloride
4 -
Eukodal® Hydrochloride
75 32
Genomorphine
82 -
Heptalgin® Hydrochloride
22 39
dl-3-Heptanone, 6-dimethylamino-4,4-diphenyl
19 13
dl-3-Heptanone, 6-dimethylamino-4,4-diphenyl, Hydrochloride
20 37
3-Heptanone, 6-(N-morpholino-)4,4-diphenyl, Hydrochloride
22 39
dl- a-3-Heptanylacetate, 6-dimethylamino-4,4-diphenyl. HCl
23 14
Heroin
79 35
Heroin Hydrochloride
80 -
dl-3-Hexanone, 6-dimethylamino-4,4-diphenyl-5-methyl, Hydrochloride
18 38
3-Hexanone, 6-piperidino-4,4-diphenyl-5-methyl, Hydrochloride
21 12
Hycodan®
72 31
Hycodan® Bitartrate
73 -
Hydrastinine Chloride
31 -
Hydrocodone
72 31
Hydrocodone Bitartrate
73 -
Hydromorphone Hydrochloride
71 -
Isoamidone Hydrochloride
18 38
Isomethadone Hydrochloride
18 38
Isoquinoline, 6,7-dimethoxy-l-(4’-ethoxy-3’-methoxybenzyl)-3-methyl Phosphate
38 -
Isoquinoline, 6,7-dimethoxy-l-veratryl
35 21
Isoquinoline, 6,7-dimethoxy-1-veratryl, Hydrochloride
36 -
Ketobemidone
14 -
Ketobemidone Hydrochloride
15 -
Ketobemidone, acetoxy, Hydrochloride
17 11
Ketobemidone, methyl
12 9
Ketobemidone, methyl, Hydrochloride
13 -
Ketobemidone, propyl
16 10
Levomethorphan Hydrobromide
51 -
Levorphan Tartrate
48 -
Meconic Acid
1 -
Meperidine
5 4
Meperidine Hydrochloride
6 -
dl-Methadone
19 13
dl-Methadone Hydrochloride
20 37
dl- a-Methadyl acetate, Hydrochloride
23 14
dl-Methorphan
49 25
dl-Methorphan Hydrobromide
50 26
l-Methorphan Hydrobromide
51 -
dl-Methorphinan
46 -
dl-Methorphinan Hydrobromide
47 -
l-Methorphinan Tartrate
48 -
Metopon Hydrochloride
74 -
dl-Morphinan, 3-hydroxy-N-methyl
46 -
dl-Morphinan, 3-hydroxy-N-methyl,Hydrobromide
47 -
l-Morphinan, 3-hydroxy-N-methyl, Tartrate
48 -
dl-Morphinan, 3-methoxy-N-methyl
49 25
dl-Morphinan, 3-methoxy-N-methyl,Hydrobromide
50 26
l-Morphinan, 3-methoxy-N-methyl,Hydrobromide
51 -
Morphine
53 -
Morphine Acetate
54 -
Morphine Hydrochloride
55 -
Morphine Hydrogen Iodide
56 -
Morphine Meconate
57 -
Morphine Sulfate
58 -
Morphine Tartrate
59 -
Morphine, benzyl
77 33
Morphine, benzyl, Hydrochloride
78 -
Morphine, diacetyl
79 35
Morphine, diacetyl, Hydrochloride
80 -
Morphine, dihydro
69 -
Morphine, ethyl, Hydrochloride
76 -
Morphine, a-monoacetyl
- 34
Morphine-N-oxide
82 -
Morphinone, dihydro, Hydrochloride
71 -
Morphinone, methyl dihydro, Hydrochloride
74 -
Morphothebaine Hydrochloride
43 -
Nalorphine Hydrochloride
83 -
Narceine
25 -
Narceine Hydrochloride
26 16
Narceine Sulfate
85 -
Narceine, ethyl, Hydrochloride
27 17
Narcotine
32 20
Narcotine Hydrochloride
33 -
Narcotine Sulfate
34 -
Neopine Hydrobromide
66 -
Nisentil®
- 6
a-Nisentil® Hydrochloride
8 7
β-Nisentil® Hydrochloride
9 8
Normorphine, N-allyl, Hydrochloride
83 -
Opianic Acid
2 -
Oxycodone Hydrochloride
75 32
Papaverine
35 21
Papaverine Hydrochloride
36 -
Papaverine Sulfate
37 -
Paveril® Phosphate
38 -
Paracodin®
70 28
Peronin
77 33
Peronin Hydrochloride
78 -
Pethidine
5 4
Pethidine Hydrochloride
6 -
Pethidine, ethyl, Hydrochloride
7 5
Pethidine, hydroxy
10 -
Pethidine, hydroxy, Hydrochloride
11 -
Phenadoxone Hydrochloride
22 39
β-Phenethylamine, 3,4,5-trimethoxy-N-dimethyl, Hydrochloride
24 15
Physeptone
19 13
Physeptone Hydrochloride
20 37
dl- a-(cis) piperidine,-1,3-dimethyl-4-phenyl-4-propionoxy
- 6
dl-a-(cis) piperidine,-1,3-dimethyl-4-phenyl-4-propionoxy Hydrochloride
8 7
dl-β-(trans) piperidine, 1,3-dimethyl-4-phenyl-4-propionoxy, Hydrochloride
9 8
Piperidine, ethyl-1-methyl-4-phenyl-4-carboxylate
5 4
Piperidine, ethyl-1-methyl-4-phenyl-4-carboxylate, Hydrochloride
6 -
Piperidine, ethyl-1-methyl-3-ethyl-4-phenyl-4-carboxylate, Hydrochloride
7 5
Piperidine, ethyl-l-methyl-4-(m-hydroxy-phenyl)-4-carboxylate
10 -
Piperidine, ethyl-1-methyl-4-(m-hydroxy-phenyl)-4-carboxylate, Hydrochloride
11 -
4-Piperidyl ethyl ketone, 4-(m-acetoxy-phenyl)-1-methyl, Hydrochloride
17 11
4-Piperidyl ethyl ketone, 4-(m-hydroxy-phenyl)-1-methyl
14 -
4-Piperidyl ethyl ketone, 4-(m-hydroxy-phenyl)-1-methyl, Hydrochloride
15 -
4-Piperidyl methyl ketone, 4-(m-hydroxy-phenyl)-l-methyl
12 9
4-Piperidyl methyl ketone, 4-(m-hydroxy-phenyl)-1-methyl, Hydrochloride
13 -
4-Piperidyl propyl ketone, 4-(m-hydroxy-phenyl)-1-methyl
16 10
Pipidone Hydrochloride
21 12
dl- a-Prodine
- 6
dl- a-Prodine Hydrochloride
8 7
dl-β-Prodine Hydrochloride
9 8
Protopine
40 23
Pseudomorphine
84 -
Pyrahexyl®
- 1
Pyran, 1-hydroxy-3-n-hexyl-6,6,9-trimethyl-7,8,9,10-tetra-hydro-6-dibenzo
-
1
1,4-Pyran, 3-hydroxy-4-oxo-2,6-dicarboxylic acid
1 -
Racemethorphan
49 25
Racemethorphan Hydrobromide
50 26
Racemorphan
46 -
Racemorphan Hydrobromide
47 -
Sinomenine Hydrochloride
52 -
Synhexyl
- 1
Thebaine
67 29
Thebaine Hydrochloride
68 30
Thebaine, acetyl demethylo dihydro, Hydro-chloride
81 36
Thebenine Hydrochloride
44 -
Trichocereine Hydrochloride
24 15
2-Tropane, 3-hydroxy carboxylic acid
- 3

Table II

PHYSICO-CHEMICAL CHARACTERIZATION OR NARCOTICS

Compound

Empirical formula

Melting point °C

Observed

Literature value

Reference

Per cent recovery (non-aqueous titration) (1)

Apomorphine Sulfate ........................
(C 17H 17O 2N) 2 H 2SO 4
230°
sample starts decomposing and gradually becomes a black mass without melting
- - 99.7
2-Azabicyclo-(3,3,1)nonane Hydrochloride
C 8H 15N HCl
205°
sample starts softening
300-302°
(2) 100 0
   
220°
sample has sintered to a greyish-white mass
288°
(3) -
   
240°
sample has become almost colourless
- - -
   
280°
sample starts to darken
- - -
   
297-299°
sample melts with decomposition
- - -
Codeine Hydrochloride
C 18H 21O 3N HCl 2H 2O
162-164°
practically all of the sample melts to a
264°
(4) 99.6
     
light yellow liquid
287°
(5) -
   
175°
recrystallization sets in
- - -
   
258-263°
sample melts with decomposition
- - -
Codeine Hydrobromide ......................
C 18H 21O 3N HBr 2H 2O
158°
sample starts to soften
190-192°
(4) 99.8
   
164-167°
sample melts partially
- - -
   
180°
recrystallization occurs
- - -
   
253-258°
sample melts with decomposition
- - -
Codeine Hydrogen Iodide ....................
C 18H 21O 3N HI 2H 2O
152-155°
-
266°
(6) 99.3
Codeine Sulfate .........................
(C 18H 21O 3N) 2 H 2SO 45H 2O
266-269°
(dec.)
-
-
100.1
Cotarnine Chloride .......................
C 12H 14O 3N Cl 2H 2O
186-188°
(dec.)
192°
(7) 100.7
Cotarnine Phthalate ........................
(C 12H 14O 3N) 2 C ?H 4(COO) 2
93.7-95.1°
practically all of the sample is melted
130°
(8) -
   
98°
recrystallization sets in
- - -
   
136-139°
sample melts to a yellow liquid
- - -
Morphine Acetate ........................
C 17H 1?O?N C 2H 4O 2 3H?O
95°
sample begins to soften
- - 99.7
   
104-108°
sample melts almost completely
- - -
   
150°
recrystallization starts
- - -
   
230°
sample discolours to a brown mass
- - -
   
246-249°
sample melts with decomposition
- - -
Morphine Meconate .......................
(C 17H 1?O 3N) 2 C 7H 4O 7 5H 2O
187-189°
(dec )
-
-
97.3
Narceine Sulfate .......................
C 23H 27O 8N H 2SO 4 10H 2O
153-156°
- - - -
Narcotine Sulfate .........................
(C 22H 23O 7N) 2 H 2SO 4 H 2O147-149°
- - - - -
Papaverine Sulfate ..........................
C 20H 21O 4N H 2SO 4
120°
sample starts to soften
- - -
   
125-133°
sample melts partially
- - -
   
140°
recrystallization sets in
- - -
   
202-206°
sample melts with decomposition
- - -

References - Table

1. Levi, L., Oestreicher, P. M. and Farmilo, C. G. Bulletin on Narcotics, 5, 15 (1953).

2. Cronyn, M. W.: Jour. Org. Chem., 14, 1013 (1949)

3. Ginsburg, D.: Jour. Org. Chem, 15, 1003 (1950).

4. Martin,F.:Jpur. Pharm. Chim ., 26,(7), 176 (1922)

5. Wilson, D C.: Pharm Jour, 113, 688 (1924)

6. Small, L. F.: Chemistry of the Opium Alkaloids. United States Government Printing Office, Washington, 1932.

7. Dott, D. B.. Pharm Jour.. 113, 688 (1924)

8. Freund, M: U.S. Patent 892,414, July 7 (1908). Chem. Abstr., 2, 2847 (1908).

References

001

Hubley, C. E.; Levi, L.: The Infrared Spectroscopic Method, Bulletin on Narcotics, VII, 1 (1955).

002

Farmilo, C. G.; Oestreicher, P. M.; Levi, L.: Common Physical Constants for Identification of Ninety-five Narcotics and Related Compounds, Bulletin on Narcotics, VI, 1 (1954).

003

Oestreicher, P. M.; Farmilo, C. G.; Levi, L.: Ultraviolet Spectral Data for Eighty-six Narcotics, Bulletin on Narcotics, VI, 3 (1954).

004

Barnes, W. H.; Sheppard, H. M.: X-Ray Diffraction Powder Data for Ninety Narcotics, Bulletin on Narcotics, VI, 2 (1954).

005

Barnes, W. H.; Forsyth, W. J.: Unit Cell, Space Group, and Indexed X-Ray Diffraction Powder Data for Certain Narcotics, Canadian Journal of Chemistry, 32, 984 (1954).