Microchemical Identification of Demerol JOSEPH LEVINE, Bureau of Narcotics Laboratory, Washington, D. C. Dernerol may bo identified microchemically through formation of crystals with alkaloidal reagonu. Doubly confirmatory test i s avsilablo with single reagent, in conjunction with scratching of test drops. Torts with picric acid, load iodide, sodium nitroprusde, potassium dichromate, and potarsium iodide are described.
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The usual procedure in meking the microchemical tests is to add a drop of the reagent to a drop of a solution of the alkaloid on a glass slide; the test drop is then allowed to stand until crystal formation tltkes place. Rubbing or stirring the tcYt drop to induce or hasten crystallisatidn is, in general, considered t.o be objectionable. Stephenson ( 6 ) states that crystals formed on stirring itre likely to be less characteristic than those formed more slowly, and recommends that stirring be %voidedt o prevent the formation of abnormal crystal forms. Scratching is sometimes recommended to induce crystallieation (%),but no reference has been found in which scratching is used t o influence the course of the crystallieation. Demcrol (ethyl-l-methyl4- phenylpiperidine - 4 - carboxylate, 5 ) may be readily identified microchemio$ly. Its reaction with 28 of the common dkaloidal reagents was studied. Of these, 5 combined to form crystals which are very well formed and suit.able for purposes of identification; 7 others f o r m e d c r y s t a l s which, either because of low sensitivity 01’ because of atypical x + crystal formation, are less suited far the purpose; 11 5formed only iEmorphous pret h cipitates; and 5 failed ta % i form any precipitate. XZ The effect of scratching tho test drop8 of Demerol and piorir acid, sodium niFigure 1. Upper Left. Dernerol-Picric A c i d troprussi~e,oT po+,amium Cryrtalr. Upper Right. Dernerol-Picric Acid iodide is v e r y striking. Cryrtals,Scratchod. Lower. Dornorol-Load Iodide Crystals Well-formed individual crystals are obtained which are entirely diffcrent in appearance from thone formed in the undisturbed test drop. They do not appear in any way t o be merely distorted or ahnormal forms of the latter, but are crystallized in distinct and unique forms which are very well suited for microscopic examimtion. Advantage may be taken of this eircumstance in having a doubly oonfirmatory test for Demerol: the formation of two distinct and individual crystal types with a single reagent, in oanjunction with the unique inthence of scratching in effecting the formation of this dual pattern of crystal types, furnishes a cross-combination of data ensuring the reliability of the identification. N o information is available a t present as to the effectiveness of the scratching technique in the identification of other alkaloids with the various alkaloidal reagents. Preliminary work indicates that fruitful results might be obtained; a study of the subject would be of decided interest.
LKALOIDS and alkaloidlike compounds, in general, combine with tho so-called “dkalaidal reagents” to form insoluble complexes, many of which crystallize in unique and characteristic forms. Moat of the natural alkaloids and many synthetic alkaloidlike compounds may be definitely idont,ified by visual microscopic examination of these crystals. Scveral books and many art,icles descriho or illustrato a number of those for which the specifioity of the micracry&aIlilline form has been established ( I , 4, 6, 8 and others).
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ANALYTICAL EDITION
or on scratching with a glass rod, were examined under a magnifieation of SOX. Best results in regard to facility of examination of the crystals, were ohtained'if the concentration of the Demerol
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, in-the case of picric acid. Here the effect of the acid a t s the formation of the characteristic X-shaped crystals.
:ryystnlline complexes were ohtained from the reaotion of Jrmerol with picric acid, potassium iodide, sodium nitroprusside, ad iodide, potassium dichromate, potassium chromate, chromic .id (the latter three in hydrochloric acid solution), potassium :roeyanide, potassium ferricyanide, platinic chloride, mercuric loride, and palladium chloride. Amorphous precipitates nly were ohtained with gold chloride, Wagner's reagent, Marme's .eagent, Mayer's reagent, phosphotungstic acid, phosphomoighdic acid, silicotungstic acid, zinc chloroiodide, sodium phosphate, sodium cobaltinitrite, and picrolonic acid. No precipitate was obtained with ferric chloride, zinc chloride, ammonium thiocyanate, saccharine, or potassium permanganate.
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suitable. In accord with the orientation of thc prisms, the hexagons may or may not appear equilateral. The relative lengths of the sides may be such that the crystals appear rhomboidal or, sometimes, diamond-shaped. POTASSIUM DlCHRo~~ATE-HYDROCHLoRIC ACID. A 5% SOhltion of potassium dichromate in a mixture of equal parts of Concentrated hydrochloric acid and water. An amorphous precipitate forms, changing t o a dense mat of long yellow needles, often in sheaves (Figure 2, l o w r left). With concentrations of Demerol under 0.2%, no amorphous preoipitate is formed; direct crystallization t&es place slowly. Scrstching hastens the erystalliaation, without affecting the crystal form. Similar crystals are formed with potassium chromate or chromic acid in hydrochloric acid solution. Neutral aqueous solutions of the three reagents produce only amorphous precipitates. POTASSIUM IODIDE, 20% t o saturated aqueous solutions. The sensitivity of this reagent varies with its concentration, A 20% solution is sensitive to a 0.2% Demerol solution, yhile sensitivity t o helow 0.05% Dernerol solutions may be obtained hy saturating a test drop of the latter with crystalline potassium iodide.
REAGENTS AND CRYSTALS BEST SUITED FOR IDENTIFICATION
PICRICACID, saturated aqueous solution. T h i s r e a g e n t is v e r y sensitive. Best results are obtained with eaneentrat.ions of Demerol of 0.1% or less. A n n m o r p h o u s preeipitatc forms, which is transformed on standing to I large rosettes, the arms of \vhieh are very h e , mavy filaments (Figure 1, u p p e ~ left). If the reaotion drop is stirred immediately after the addition of the solut i o n s , X - s h a p e d crystals form (Figure 1,upper right). \Yith higher concentrations of Demerol, hoth forms of crystals may be found in the same test. drop after ncratehing. If the Demerol is dissolved in 0.1 3- hvdroc h l o r i c a c i d i n s t e n d of water no X-shaped crystals &ill form, even on scratching. Instead, therc are formed, in addition to Figure 2. Upperleft. Domorol-Sodium Nitroprurrosettes, long very fine, Dernerol-Sodium ride Crystals. Upper Right. needles. A d h i t i o n of a NitroprurrideCryrtair,Scratchod. Lower. Demorolv e r y small a m o u n t of Potassium Dichromate Crystals sodium bicarbonate t o the Demerol solution promotes the formation' ofCX's; if larger amounts of sodium bicarbonate are usod, Some crystals uf this type may form even in the undisturbed drop. L ~ n IODIDE o prepared by the method of Wagenanr (7). Add to a 1 t o 3 aqueous potaskum acetate solution a. drop of methyl red indicator, then acetic acid until the yellow color changes t o light brown. Sntur.zte v i t h lead iodide while warming gently, cool, and filter. With a 0.1% solution of Demerol, an amorphous pmcipihte forms, ohmging to rosettes, the arms of nhich broaden on standing to form long flat plates (Figure 1, lower left). The rosettes lie in a horizontal plnne, and overlie other rosettes lying in different planes. If the test drop is scratched, short flat rods which look like the arms of the rosettPs form along the scratch proper, while throughout the drop the same types of rosettos as in the undist.urhed test drop crystallize quickly. SODIUM NITROFRUSsIDE, 5% aqueous Solution. With a 1% solution of Demerol, an amorphous precipitate forms, changing t o long coarse bledelike plates, bath individual and twinned (Figure 2, upper left). With solutions of lower concentration, no amorphous precipitate forms initially; the crystals slowly form from the edge nf +ha rlrnn Y."~ If the test drop is scratched, small very distinct hexagonal prisms are formed (Figure 2, upper right). Concentrat,ions of 0.2 to 1% Demerol ~ i e
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INDUSTRIAL A N D ENGINEERING CHEMISTRY 7
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