Tropine hydrochloride

Preparation of Di-n-Propyl Acetyl Tropine Hydrochloride Tropine (11.12 grams) was dissolved in 100 ml of anhydrous pyridine and to this solution was added 15.64 grams of din-propyl acetyl chloride. The mixture was refluxed for 6 hours. This solution was then cooled and the pyridine removed in vacuo. The residue was dissolved in chloroform. The chloroform solution was washed with 10% hydrochloric acid to remove the residual trace of pyridine. The hydrochloride of the product ester is soluble in chloroform and is not extracted from chloroform by hydrochloric acid. This is an unexpected property. 

Atropine (XXVIII) had already been prepared from ( + )-acetyltropoyl chloride and tropine (40) followed by resolution (41), using n-camphor-sulfonic acid, to obtain first the salt of dextrorotatory hyoscyamine. Recently dibenzoyltartaric acid was claimed to precipitate the salt of the ( —)-antimer first (42). Direct synthesis of hyoscyamine (XXVIII) was realized by melting S-( — )-acetyltropoyl chloride (XXXV), obtained for the first time in crystalline form, with tropine hydrochloride (XXXVI), followed by acid deacetylation of acetylhyoscyamine (XXXVII)... 

The esterification can be also performed by treating tropine hydrochloride with (-)-acetyltropyl chloride in nitrobenzene (24). 

Tropine hydrochloride 60 was transformed into the corresponding chloroformate 61 in 98% yield with diphosgene [40]. 

Azabicyclo[3.2.2]nonane, 40B, 284 3-Azabicyclo[3.3.1Jnonane hydrobromide, 29, 507 Tropine hydrobromide, 18, 698 Tropine hydrochloride, 18, 698... 

Ci5H2oClN02r 0 Benzoyl- ( -tropine hydrochloride, 44B, 527 Ci5H2oClN02r O-Benzoyltropine hydrochloride, 42B, 449 C15H20IN3O9 0.5 CHflO, 6,11-Diacetylanhydrotetrodotoxin hydroiodide methanol solvate, 31B, 241... 

Dihydroxytropane, CgHijO N. This base was isolated from the mixture of hydrolysed bases obtained in working up the alkaloids of Java coca it occurs in the fraction less soluble in ether than tropine and Zr-tropine, has m.p. 209-209-5°, — 22° (EtOH), yields a hydrochloride, [a] ° + 1-75°... 

Tropacocaine (Benzoyl-ili-tropeine), CuHj gOgN, was discovered by Giesel in Java coca leaves and has since been found in Peruvian coca. Its preparation from the former source has been described by Hara and Sakamoto, It crystallises in needles, m.p. 49°, is insoluble in water, but soluble in alcohol, ether or dilute ammonia and is generally prepared by benzoylating /t-tropine, and purified as the hydrochloride. Its alcoholic solution is alkaline and optically inactive. The hydrochloride forms needles, m.p. 271° (dec.), and the hydrobromide leaflets. The aurichloride separates in minute yellow needles, m.p. 208°, from hot aqueous solutions the picrate has m.p. 238-9°. When heated with hydrochloric acid or baryta water the alkaloid is hydrolysed to benzoic acid and -tropine. ... 

Take the total amount of succinaldehyde (obtained from 4 of the above syntheses combined) and without further treatment or purification (this had better be 15.5 g of succindialdehyde) put into an Erlenmeyer flask of 4-5 liters capacity. Add 21.6 g of methylamine hydrochloride, 46.7 g of acetonedicarboxylic acid, and enough water to make a total volume of 2 liters. Adjust the pH to 8-10 by slowly adding a saturated solution of disodium phosphate. The condensate of this reaction (allow to set for about 6 days) is extracted with ether, the ethereal solution is dried over sodium sulphate and distilled, the product coming over at 113° at 25 mm of pressure is collected. Upon cooling, 14 g of tropinone crystallizes in the pure state. Tropinone can also be obtained by oxidation of tropine with potassium dichromate, hut I could not find the specifics for this operation. 

Tropine (34.24 g) is treated with anhydrous diethyl ether and ethereal hydrogen chloride and the precipitated hydrochloride is isolated by evaporation of the solvent. 3,5-Dichlorobenzoylchloride (51.7 g) is added and the mixture stirred at 140°C for 15 minutes during which time the mixture liquifies, evolves hydrogen chloride gas and resolidifies. After heating for a further 15 minutes the cooled solid is dissolved in water, an excess of an aqueous solution of potassium carbonate is added, and the base is extracted with ethyl acetate. Evaporation of the dried ethyl acetate solution yields a solid, which is recrystallized from aqueous methanol to yield 3,5-dichlorobenzoic acid 8-methyl-8-aza-bicyclo[3.2.1]oct-l-yl ester (endo). MP 95°C (51.8 g). 

Pharm Class Anticholinergic Chemical Name D-Tropine tropate CAS Num 55-A7-0 (hydrochloride)... 

The base thus obtained is distilled in vacuo and crystallised from a mixture of benzene and light petroleum. About 65% of pseudotropine (m.p. 108°) is obtained, and 35% of a mixture of tropine and pseudotropine, which is mixed with the next batch of tropine to be converted. It is benzoylated in the same way as has been described under cocaine (Barrowcliff and Tutin, J.C.S. 1909, 95, 1970), and the resulting tropacocaine hydrochloride purified by recrystallisation from petroleum. M.p. 271° (Wllstater) 283° (Barrowcliff and Titin). 

Atropine can be synthesized from tropi-none and tropic acid as starting materials. Tropinone can be prepared by Robinson s synthesis (68) and reduced under proper conditions to tropine. ( )-Tropic acid can be prepared from ethyl phenylacetate (69, 70) or acetophenone (71). The 0-acetyl derivative of tropyl chloride reacts with tropine to yield O-acetyl of atropine hydrochloride, from which the acetyl group hydrolyzes spontaneously in aqueous solution (72). 

Bellaradine (C7H13ON) (225), an oily base isomeric with nortro-pine, is present to the extent of 0.008% along with Z-hyoscyamine, Z-scopola-mine, and tropine in Bulgarian belladonna root. Its strong basic properties were employed in its separation from this mixture of alkaloids. It forms a crystalline and weakly Zeyorotatory hydrochloride which, like tropinone and... 

Scopolamine produces the same effects in the eye as atropine, but is more powerful. It is usually administered as its hydrobromide, and a 0.2 % solution of this salt can be used instead of 1 % atropine. sulfate. The semisynthetic mandelic ester of tropine, homatropine, is useful as a transitory mydriatic. Both its mydriatic and cycloplegic effects are weaker than those of atropine and much shorter in duration. It is used as its hydrochloride or hydrobromide in 1-2 % solution. 

It is curious that Jowett and Pyman did not prepare benziloyltropeine, since benzilic acid contains the groups, phenyl and alcoholic hydroxyl, which they had found to confer high activity on esters of tropine this ester was studied by Benda and Kraupp (17a) who found that its hydrochloride was as active as atropine sulphate on the cat eye and had, if anything, a slightly more prolonged effect. Kreitmair s results (14) with benziloyl- -tropine have already been mentioned, and several mydriatic benzilic esters of alkamines simpler than tropine will be mentioned later. 

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