Chloroform Atropine

Treatment of atropine (26) with trichloroethyl chloroformate leads to the formation of a mixture of compounds 194 and 195, which when treated with zinc dust in acetic acid yields noratropine (21) (103) (Scheme 18). Similarly, the... 

Hypotensive activity. Essential oil, administered intravenously to dogs at a dose of 3 p,L/kg, was active. The ethanol (70%) extract, administered intravenously to dogs at a dose of 75 mg/kg, was active. There was a dip followed by rise in blood pressure° . Ethanol (80%) extract of the aerial parts, at a dose of 10 mg/kg, was not blocked by atropine. The extract did not inhibit pressor response of norepinephrine either . Ethanol (95%) extract of the seed, administered intravenously to dogs at a dose of 10 mg/kg, produced a transient effect that was blocked by atropine ". Petroleum ether fraction chromatographed and fraction eluted with chloroform, administered intravenously to rabbits at a dose of 0.80 mg/kg, was inactive. Methanol extract, administered intravenously to dogs and rabbits at a... 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylic acid monohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, ododess, crystalline powder that melts at 220—226°C. It is soluble in methanol, sparingly soluble in ethanol and acetone, slightly soluble in water and isopropyl alcohol, freely soluble in chloroform, and practically insoluble in ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropine to discourage abuse. 

Atropina Atropine, C17H23N03, white, acicular crystals, odorless, of bitter taste and alkaline reaction very soluble in alcohol and in chloroform, also soluble in 130 of water at 59°F. It is decomposed by prolonged contact with caustic alkalies and is resolvable into tropine and tropic acid. 

Atropin was obtained from belladonna roots and by racemisation of L-hyoscyamine with dilute alkali or by heating in chloroform solution. The alkaloid was crystallised from alcohol on addition of water, or from chloroform on addition of light petroleum, or from acetone in long prisms, m.p. 118°C, sublimed unchanged when heated rapidly. It is soluble in alcohol or chloroform, less soluble in ether or hot water, sparingly so in cold water (in 450 L at 25°C) and almost insoluble in light petroleum. Atropine is optically inactive. 

Alkaloids fraction was obtained from roots by extraction with benzene. First of all the atropine was isolated. Then after isolation of the atropine, the extract containing the scopolamin and other alkaloids was washed by slightly acidic solution (this solution was acidified with the hydrochloric or acetic acid). To the acidic solution the potassium carbonate was added, then scopolamin was extracted with chloroform, ether or their mixture. The organic extracts were combined and evaporated under reduce presser. Concentrated residue was washed with water, filtered and dried. 

Atropine does not occur as such in the solanaceae plants but is formed from the hyoscyamine present by treatment with dilute alkalies, when isomerization takes place and the inactive form of the alkaloid is obtained. It is crystalline, m.p. 115.5°, and only slightly soluble in water but soluble in alcohol and chloroform. The salts are crystalline and soluble in water. 

Cai et al. first used a chloroform-0.07 M sodium phosphate buffer (pH 6.4-6.5) solvent system for the separation of matrine and oxymatrine from Sophora flavescens, atropine, scopolamine, and hyoscyamine from Datura mete L. by HSCCC. Cooper et al. successfully used chloroform-0.2 M potassium phosphate buffer with an optimum pH value of each at 5.0, 5.6, 6.0, and 7.4 for the separation of pyrrolizidine alkaloids from various sources of Senecio douglasii var. longilobus, Trichodesma incanum, Symphytum spp. and Amsinckia tessellata, respectively. 

In extraction procedures using methylene chloride as organic phase, bromothymol blue has been used as an ion-pairing counterion for amfetamine, and picrate ions for atropine. Tetrabutylammonium ion has been used for the extraction of penicillins into chloroform. 

Ipratropium Bromide. Ipratropium bromide, 3-(.Thy-droxy-l-oxo-2-phenylpnopoxy)-8-methyI-8-(l-methylethyl,-8-a/oniabicyclo[3.2.l oclanc bromide (Atrovent). is a quaternary ammonium derivative of atropine. It is freely soluM in water and ethanol but insoluble in chloroform and ether. The salt is stable in neutral and acidic solutions but lapiiU hydrolyzed in alkaline solutions. 

Atropine was discovered in 1831 in the roots of the belladonna plant, and is a strongly poisonous alkaloid. Its chief use in medicine depends upon its action in dilating the pupil and paralysing the accommodation of the eye, and it is also used to check the inhibition of the heart arising from administration of chloroform and the depressant action of morphine on the respiratory centre. 

Atropine crystallises in colourless acicular crystals M.p. 115.5°. It dissolves in 450 parts of water at 25° and in 87 parts at 80° in 3 parts of 90% alcohol and in 1 part of chloroform. It should be optically inactive and no colour should be developed on treatment with sulphuric acid. 

The ethyl ether solution of bases is dehydrated with anhydrous sodium sulfate, filtered and the ether concentrated and cooled to crystallize a mixture of hyoscyamine and atropine. The mixture is mixed with one quarter its weight in chloroform and refluxed at 116° to 120° for 2 hours. The racemization of hyoscyamine produces atropine. 

Conventional methods of alkaloid isolation are used to obtain a crude mixture of atropine and (-)-hyoscyamine from the plant products. This crude mixture of alkaloids is racemizedto atropine by refluxing in chloroform or by treatment with cold dilute alkali (67). 

A quantity of alkaloidal solution or tablets containing between 1.6 to 2.4 mg of atropine is rendered alkaline and extracted with chloroform. The alkaloid is re-extracted from the chloroform with 6% acetic acid and ethanol. An exact aliquot of the resulting extract is transferred into an evaporating dish and evaporated just to dryness on a water bath, fuming nitric acid (0.2 ml) is immediately added to the residue and again evaporated to dryness. The resulting residue is dissolved in acetone (about 3 ml) and made up to volume (10 ml). A 3.0% potassium hydroxide in methanol (0.1 ml) is added and the mixture allowed to stand for 5 minutes. A purple color is developed and the intensity of this color is then measured in a photoelectric absorptiometer. The con-... 

In the first procedure, hyoscyamine (or atropine) can be selectively determined in the presence of scopolamine by using bromcresol purple, which forms a chloroform-extractable complex with hyoscyamine at pH 6.6. This complex is separated and measured at 420 nm. Scopolamine and the hydrolytic product tropine do not interfere. 

A fluorimetric method for the determination of atropine and other related alkaloids has been described (99). The method is based on the formation of fluorescent complex between atropine and eosine To a solution of atropine in chloroform (9 ml) 0.1% eosine solution is added (1 ml). The mixture is shaken thoroughly and the fluorescence intensity at 556 nm (excitation at 365 nm) is measured after 10 minutes. Beer s law is obeyed with 1 to 5 pg of atropine per ml the coefficient of variation is 2.6%. 

Wyatt et al. worked out a GLC assay for atropine and scopolamine in belladonna extract. The extract was solved in 0.1 N sulphuric acid, homatropine hydrobromide was added to this solution as an internal standard, and interfering materials were extracted from the acidified solution with chloroform - and finally a mixture of chloroform and 2-propanol (10 3) if there is an emulsion problem. The alkaloids were subsequently extracted into chloroform (or chloroform-2-propanol) from the basified aqueous layer (pH 9.5 phosphate buffer was used instead of mineral alkali to minimize ester cleavage) and the chloroform extracts were filtered through anhydrous sodium sulphate (previously washed with chloroform). 87 % of the alkaloids were recovered in the first extract, so that two additional extractions gave suffi-... 

Column Silica gel SilOO 5 pm (100x3 mm ID) impregnated with 0.06 M picric acid (pH 6), mobile phase chloroform saturated with the stationary phase 0.06 M picric acid, flow rate 0.2 ml/min, detection UV 345 nm. Peaks 1, dodecylbenzene (t ) 2, apoatropine 3, ergotaminine 4, atropine 5, ergotamine 6, scopolamine. 

The separation of atropine, Z-hyoscyamine and Z-scopolamine has been effected by the fractional crystallization of their aurichlorides. It has been pointed out, however, that the solubility relations of these derivatives are dependent upon impurities and the relative amoimts of each present in the mixture (50). The bases may be recovered by decomposing an aqueous solution of the aurichloride with hydrogen sulfide and filtering to remove the gold sulfide. The base is liberated by addition of potassium carbonate to the filtrate and extraction with chloroform. An alternate method for the separation of atropine and Z-hyoscyamine (25) is by fractional crystallization of their oxalates from acetone and ether in which the Z-hyoscyamine derivative has the greater solubility. Z-Scopolamine and dioscorine on the other hand are purified through their insoluble hydrobromides. 

Atropin forms colorless, silky needles, which are sparingly soluble in cold water, more readily soluble in hot water, very soluble in chloroform. It is odorless, but has a disagreeable, persistent, bitter taste. It is distinctly alkaline, and neutralizes acids with formation of salts. One of these, the sulfate—Atropinse sulphas, IT. S.—is a white, crystalline powder, readily soluble in water, which is the form in which atropin is usually administered. 

Qu et al.[30] determined atropine sulphate by FI solvent extraaion based on ion-pair formation with Bromocresol Green and extraction into chloroform. A sampling frequency of 60 h and a precision of 0.7% r.s.d. were reported. 

Carbon-13 n.m.r. and mass spectrometry have become essential methods in quantitative analysis of alkaloid mixtures extracted from plants, in addition to g.l.c. and photometry. Study of the mechanism of fragmentation of 3-substi-tuted tropanes is a useful tool for analysis of mixtures of tropane alkaloids. A comprehensive study on the n.m.r. spectroscopy of tropane alkaloids included most major representatives of this class. Other papers deal with the n.m.r. spectra of cocaine metabolites and derivatives. A radioimmunassay of atropine and benzoylecgonine in urine was published. Photometric determination of tropane derivatives in chloroform extracts was done via colorimetry of the bromocresol purple complex.Adsorption chromatography methods have been used with different resins. ... 

CiiHi NjOa, Mr 208.26, oily liquid or crystals, mp. 34 °C (as hydrochloride 193-205 °C, nitrate I74°C), bp. 260°C (0.7 kPa), [a] > +106° (HjO), soluble in water, ethanol, chloroform forms well crystallizing salts with acids. P. is the main alkaloid of the South American jaborandi tree (Pilocarpus jaborandi). It is isolated from the leaves. P. is also easily accessible by synthesis and is used as its salts in medicine as a cholinergic parasympathicomimetic, miotic (for glaucoma) agent and as an atropine antagonist it is also used in veterinary medicine for colics and constipation. Detection by means of Helch s reaction. Pilocarpus species contain further imidazole alkaloids (see table). 

Pig. 152. Separation of an alkaloid mixture on a gradient layer. Left of diagonal spacer acid alumina for TLC (Firm 153) -j- 10% gypsum right basic alumina for TLC (Firm 153) + 10% gypsum. Solvent chloroform-methanol (95 +5) CS length of run 15 cm a contaminant alkaloid ( ) has separated below the atropine... 

PoETHKE et al. [125, 173] have worked with belladonna herbs and tinctures. They used silica gel G and chloroform-acetone-diethylamine (50 + 40 + 10) as solvent. Oswald and Flhck [151—153] have chromatographed hyoscyamine and other alkaloids from this material, notably belladonnine, apoatropine, aposcopolamine, scopine and scopoline. Six solvents were used, of which the best was found to be butanone-methanol-7.5% ammonium hydroxide (60 + 30 + 10) the Dragendorff reagent was employed for detection. The method was worked out also for quantitative determination (planimetric evaluation) (limit of error 5.8%). A linear relation was found between spot area and amount of alkaloid, provided that the amount of substance did not fluctuate by more than 20%. In this way it was possible to determine the mixture of hyoscyamine and atropine in the presence of scopolamine (hyoscine) in some of the plant organs of Atropa belladonna. Datura stramonium, Hyoscyamus niger and H. muticus [153]. 

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