Chlorides hydrochloride salts

Chloride-hydrochloride salt of thiamine 4087 Chloroethene homopolymer 3082... 

Synonyms Aneurine hydrochloride Thiamin chloride Thiamine chloride hydrochloride Thiamine dichloride Thiamine hydrochloride Thiamin hydrochloride Thiaminium chloride hydrochloride Vitamin Bi hydrochloride Definition Chloride-hydrochloride salt of thiamine Empiricai C12H18CI2N4OS Formuia C12H17CIN4OS HCI Properties Small wh. cryst. orcryst. powd., nut-like odor sol. in water, glycerol si. sol. in alcohol insol. in ether, benzene m.w. 337.30 m.p. 248 C (dec.)... 

A special type of ammonio group is represented by 4-( 1 -pyridinium)-pyridine and other azinium analogs. Such products often result from self-quaternization of highly reactive derivatives. A -(4-Pyridyl)-and A -(3-nitro-4-pyridyl)-pyridinium chloride hydrochlorides (121) react with aniline, chloride ion, and water to give 4-substituted pyridines plus pyridine. l-(2-Quinolyl)- and l-(4-quinolyl)-pyridinium salts undergo 2- and 4-substitution, respectively, with amines, anilines, hydroxylamine, phenols, alkoxides, mercaptans, and chloride... 

A solution of 24.6 g of o-allyl-epoxypropoxybenzene dissolved in 250 ml of absolute ethanol saturated with ammonia was placed in an autoclave and heated on a steam-bath for 2 hours. The alcohol was then removed by distillation and the residue was redissolved in a mixture of methanol and ethylacetate. Hydrogen chloride gas was introduced into the solution. The hydrochloride salt was then precipitated by the addition of ether to yield 11.4 g of product. Five grams of the amine-hydrochloride thus formed were dissolved in 50 ml of methanol and 9 ml of acetone. The resulting solution was cooled to about 0°C. At this temperature 5 g of sodium borohydride were added over a period of 1 hour. Another 2.2 ml of acetone and O.B g of sodium borohydride were added and the solution was kept at room temperature for 1 hour, after which 150 ml of water were added to the solution. The solution was then extracted with three 100-ml portions of ether which were combined, dried over potassium carbonate, and evaporated. The free base was then recrystallized from petrol ether (boiling range 40°-60°C) to yield 2.7 g of material having a melting point of 57°C. 

The corresponding hydrochloride was prepared by dissolving 2 g of the product, prepared above, in 20 ml of acetone, and adding to the resulting solution acetone saturated with hydrogen chloride until the pH was reduced to about 3. The precipitated hydrochloride salt was then recrystallized from acetone. 

A mixture of 16.3 g of (2-chloro-5-methylphenyl)glycidic ether (from epichlorohydrin and 2-chloro-5-methylphenol) and 6.2 g of t-butylamine in 50 ml of ethanol is heated at reflux for 6 hours. The solvent is removed, the residue Is washed with water and then extracted with benzene. The dried extract is evaporated to give 1-t-butylamino-3-(2-chloro-5-methylphen-oxy)-2-propanol. Treatment of the free base in benzene solution with dry hydrogen chloride yields the hydrochloride salt. 

A mixture of 20 g of 1. [p.((3.diethylaminoethoxy)phenyl]-1,2-diphenylethanol in 200 cc of ethanol containing an excess of hydrogen chloride was refluxed 3 hours. The solvent and excess hydrogen chloride were removed under vacuum, and the residue was dissolved in a mixture of ethyl acetate and methylene chloride. 1-[p-((3.diethylaminoethoxv)phenyl] -1,2-diphenylethylene hydrochloride was obtained, melting at 148° to 157°C. This hydrochloride salt was treated with N-chlorosuccinimide in dry chloroform under reflux. The product then obtained was converted to the free base and treated with citric acid. The dihydrogen citrate salt of 1-[p-((3-diethylaminoethoxy)phenyl]-1,2-diphenylchloroethylene was obtained, melting at 116.5° to 118°C. 

The N-[/3-(o-chlorophenyl)-/3-hydroxyethyl] -isopropylamine obtained by the foregoing procedure was dissolved in about 3 liters of ether and dry hydrogen chloride gas was bubbled into the solution until it was saturated, whereupon the hydrochloride salt of N-[/3-(o-chloro-phenyl)-/3-(hydroxy)-ethyl] isopropylamine precipitated. The salt was separated from the ether by filtration, and was dissolved in two liters of anhydrous ethanol. The alcoholic solution was decolorized with charcoal and filtered. 

The basic ester may be dissolved in anhydrous ether and then precipitated by adding a slight excess of a solution of dry hydrogen chloride in ether and the hydrochloride salt may be isolated as an amorphous, glasslike product, which could be crystallized from anhydrous acetone or from methanol-ether. In this manner there was obtained as a stable, crystalline, colorless substance -dimethylaminoethoxyethyl phenothiazine-10-carboxylate hydrochloride, one sample of which melted at 161°-163°C with decomposition. 

The free base is liberated from the acid solution with 20% sodium hydroxide solution and taken up in ether. The ether layer is washed with water, saturated with NaCI and then shaken with solid potassium hydroxide. The ether is removed by distillation, 200 parts of benzene added and distilled off. The residue is distilled in vacuo and the fraction 150°-165°C/2 mm is collected and amounts to 433 parts. The hydrochloride salt is prepared by dissolving the free base in anhydrous ether and slowly adding an alcoholic solution of hydrogen chloride. The solid is recrystallized from absolute alcohol-ether mixture or isopro-panol-ether mixture and has a MP of 161°-162°C. 

On evaporation of the ethyl ether from the ethyl ether solution, the benzhydryl ether was recovered as a pale yellow oil. The benzhydryl ether was dissolved in 60 ml of isopropanol and the isopropanol solution acidified to a pH of 3 with dry hydrogen chloride-methanol solution. The acidic propanol solution was then diluted with ethyl ether until a faint turbidity was observed. In a short time, the crystalline hydrochloride salt of the benzhydryl ether separated from the propanol solution. The crystallized salt was recrystallized once from 75 ml of isopropanol with the aid of ethyl ether in order to further purify the material. A yield of the pure hydrochloride salt of 1-methylpiperidyl-4-benzhydryl ether of 24.5 grams was obtained. This was 39% of the theoretical yield. The pure material had a melting point of 206°C. 

To the reduction mixture was then added 3.5 g of 5% palladium on carbon catalyst and the mixture was hydrogenated under a hydrogen pressure of 50 psi at room temperature for 12 hours. The catalyst was removed by filtration and the filtrate was evaporated to a small volume. The concentrated filtrate was dissolved in diethyl ether and the ethereal solution was saturated with anhydrous hydrogen chloride. The reduction product, 3,4-dimethoxy-N-[3-4-methoxyphenyl)-1 -methyl-n-propy 11 phenethylamine was precipitated as the hydrochloride salt. The salt was filtered and recrystallized from ethanol melting at about 147°C to 149°C. 

To a solution of 28 g (0.1 mol) 2-carbethoxymethylene-3-methyl-5-bromo-4-thiazolidinone prepared as described In 200 ml benzene Is added (0.2 mol) piperidine and the mixture is allowed to stand for 3 hours at 25°C. The resulting suspension is filtered to remove the precipitated piperidine hydrobromide and the filtrate is evaporated to dryness. The residue is taken up in ether, filtered and the filtrate saturated with dry hydrogen chloride to yield the hydrochloride salt of 2-carbethoxymethylene-3-methyl-5-piperidino-4-thiazolidinone, MP 158°C to 159°C. 

The hydrochloride salt was precipitated as an oil from an ethereal solution of the base with ethereal hydrogen chloride. It was crystallized from butanone MP 170° to 171.5°C. 

To make the hydrochloride salt, the bisacetamide or, by another name, 1,11-diphenyl-2,2,3,9,10,10-hexamethyl-4 3hydroxy ethyl )-3,6,9-triazaundecane is dissolved In n-butanol. The solution is chilled and then dry hydrogen chloride gas is passed into the solution causing an oil to separate. To the heavy oil ether is added and then stirred causing crystallization to occur. MP146°Cto 147°C. Analysis for nitrogen calc. 8.3%, found 8.2%. 

The hydrochloride salt of this amine was prepared by dissolving the amine in ether and adding ethereal hydrogen chloride to the ether solution. The solid hydrochloride salt which precipitated was racrystallized from an ethanol-ether mixture and was found to melt at 154°-155°C. 

B.5 parts of 1 -azaphenothiazine carboxylic acid chloride and 14 parts of piperidino-ethoxy-ethanol were introduced into 100 parts of chlorobenzene and the mixture boiled under reflux for 5 minutes. After cooling off the precipitated hydrochloride salt of piperidino-ethoxy-ethanol was filtered off on a suction filter. Water was added to the filtrate and the pH thereof adjusted to 5 to 6 with dilute HCI. The aqueous phase was then removed, a caustic soda solution added thereto and then extracted with ether. The ethyl extract waswashed with water, then dried with potash and the ether distilled off. 9.4 parts of the piperidino-ethoxy-ethyi ester of 1 -azaphenothiazine carboxylic acid were obtained. This product was dissolved in 20 parts of isopropanol and the solution neutralized with isopropanolic HCI. The monohydrochloride which precipitated out after recrystallization from isopropanol had a melting point of 160°Cto 161°C. 

There are other soUd states which sometimes confuse the measurement and definition of solubiUty. The dmg may crystaUize as a hydrate, i.e. under inclusion of water molecules. If the hydrate form is more stable than the pure form it may be difficult to measure the intrinsic solubility of the drug at all. Often drugs tend to precipitate in an amorphous form, often under the inclusion of impurities. As with metastable polymorphs, such amorphous precipitates may lead to erroneously high solubility measurements. CommerciaUy, drugs are often crystallized in salt form, e.g. as the hydrochloride salt, a cation with a chloride anion. In these co-crystallized salts, a much lower solubility than the intrinsic solubility will typi-... 

Many years ago, L. F. Audrieth studied numerous reactions of amine hydrochloride salts. These compounds contain a cation that is a protonated amine that can function as a proton donor. Consequently, the molten salts are acidic and they undergo many reactions in which they function as acids. This behavior is also characteristic of ammonium chloride as well as pyridine hydrochloride (or pyridinium... 

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