Solubility hydrochloride

Table 13 shows some of the developmental products that have EPA appHcations pending and may be available in the near future. Sea Nine is a variation on the very successflil isothiazolone chemistry. It is claimed to be an improvement over metallic actives used for antifouling paint and wood preservation (46,47). Decylthioethylamine and its water-soluble hydrochloride are claimed to be especially effective at controlling biofilm in cooling water appHcations (48—50). The hydroxymethylpyra2ole shown is also suggested to have properties that are well suited to the protection of aqueous products or emulsions (51,52). 

The free base tends to become oxidized in the air but may be preserved as the hydrochloride. This is prepared by transferring it as soon as possible to 1500 cc. of distilled water containing 100 cc. of concentrated hydrochloric acid. The sparingly soluble hydrochloride separates at once. It is recrystallized from the mixture with the use of a little decolorizing carbon, whereupon it separates as colorless needles. A further crop is obtained on concentrating the mother liquor under reduced pressure to about 200 cc. The yield is no g. (82.1 per cent of the theoretical amount). 

Tuduranine, CjgHjgOgN. This member of the aporphine group (p. 306) is the most recent addition to Sinomenium alkaloids and was isolated by Goto from the mother liquors of sinomenine. It is crystalline, has m.p. 125° (with softening at 105°), and yields a sparingly soluble hydrochloride, m.p. 286° (dec.), [a] f — 148° (dilute MeOH), is freely soluble in alkali, and gives feeble ferric chloride and diazo-colour reactions and a fuchsin-red colour with formaldehyde and sulphuric acid. It behaves as a secondary base and yields a diacetyl derivative, m.p. 170°, [a] / — 321-71° (MeOH), which does not form a methiodide, but can be hydrolysed to A -acetyl-tuduranine, m.p. 277°, — 395-24°, and this can be methylated to... 

Amine or Base may be separated from the majority of insoluble organic substances by shaking it with dilute hydro-rhloiic acid, with which it forms the soluble hydrochloride. 

The hydrochloric acid is removed by the strong tertiary base, methyldibutylamine, which has a soluble hydrochloride. In B.P. s 631,549 and 652,981 it was shown that compound (II) could be prepared by the action of dimethylamine on P0C13 in chloroform containing an excess of methylbutylamine. The further reaction with water is very conveniently carried out in the same system by adding an excess of aqueous sodium hydroxide solution. The chloroform layer contains the tertiary amine and (I). The solvent and amine are stripped off leaving the product. Side reactions take place, and the commercial product also contains some triphosphoric pentadimethylamide (I A) and smaller amounts of other phosphoric amides. The compound (I A) is itself also a valuable systemic insecticide. 

Meperidine (isonipecaine, Demerol , and Dolantin ) is the methyl ester of methyl-4-phenylpi-peridine-4 carboxylic acid. It is used in the form of its soluble hydrochloride. The piperidine nucleus is also present in many alkaloids, such as atropine or lobeline, which are not analgesics, as well as in morphine. 

The basicity of an amine can be used for purification. The amine is initially more soluble in ether than in water. Addition of dilute HC1 converts it to the water-soluble hydrochloride salt. Neutralization with NaOH regenerates the free amine. 

The reduction of acid chlorides may proceed at lower temperatures in the presence of a tertiary amine or sodium acetate. Peters and van Bekkum improved the method of Sakurai and Tanabe,260 using ethyldiisopropylamine, instead of A(7V-dimethylaniline, as a HC1 acceptor.261 Ethyldiisopropylamine had the advantage of forming an acetone soluble hydrochloride, and workup of the reaction mixture was easier when acetone was used as solvent. Reductions in the presence of these basic substances have been found to be especially effective when the acid chlorides are labile to decarbonylation. Examples of the use of base are shown in eqs. 13.139261 and 13.140.262 When the original procedure of the Rosenmund reduction was applied to 1 -/-bulylcyclohcxanc-carbonyl chloride, f-butylcyclohexanc was the sole product, compared to greater than 95% yield of the corresponding aldehyde in the presence of ethyldiisopropylamine or sodium acetate.261... 

Carbonyl platinum dichloride has a distinctly basic character. It dissolves in excess of hydrochloric acid to a lemon-yellow solution, due, perhaps, to the formation of a soluble hydrochloride, PtCl2.CO.HCl. This solution is a powerful reducing agent, effecting the reduction of silver, gdld, and mercury from their salts.1 The monocarbonyl unites with soluble metallic chlorides, such as those of the alkali metals, to yield yellow, crystalline double salts. These, however, are so readily soluble and so easily decomposed that their satisfactory isolation has proved difficult. With the chlorides of certain organic bases, however, well-defined compounds have been obtained.4... 

Under such conditions, the drugs will form water-soluble hydrochloride salts. These can then be selectively extracted into the aqueous acid, thus reducing potential contamination by chlorophylls, carotenoids, fats and other lipophilic materials which are problematic in the analyst of plant materials. 

This reaction can, if necessary, be run on five times the indicated scale. Dissolve about 0.1 g of tin(ll) chloride in 0.2 mL of concentrated hydrochloric acid, add a small quantity of the azo compound (20 mg), and heat. A colorless solution should result and no precipitate should form on adding water. The aminophenol or the diamine products are present as the soluble hydrochlorides the other product of cleavage, sulfanilic acid, is sufficiently soluble to remain in solution. 

Formation of soluble hydrochlorides of basic drugs does not necessarily result in improved bioavailability as was illustrated by comparative absorption studies of tetracyclines and lincomycin and their salts. " " Tetracycline-free bases gave higher plasma levels than their hydrochloride salts, while lincomycin hydrochloride had a lower bioavailability than the hexadecylsulfa-mate salts. These differences have been attributed to a common ion effect with gastric HCl following oral administration. 

Clindamycin is absorbed rapidly from the gastrointeslini tract, even in the presence of food. It is available as ibt crystalline, water-soluble hydrochloride hydrate fhyclak. and the 2-palmitate c.stcr hydrochloride salts in oral dosigi forms and as the 2-phosphatc e.stcr in solutions for intramuv cular or intravenous injection. All forms arc chemically voi ssAwVvaw brj % aiic. 

Antazoline is less active than most of the other anlihisla-minic drugs, but it is characterized by the lack of local irritation. The more soluble phosphate salt is applied topically to the eye in a 0.5% solution. The less soluble hydrochloride is given orally. In addition to its use as an antihistamine, antazxtline has more than iwice the local anesthetic potency of procaine and also exhibits anticholinergic actions. 

Burgstahler et al. diazotized the sparingly soluble hydrochloride of 3,4-di-r-butylaniline at O-S", treated the filtered solution with sodium fluoroborate, and obtained the diazonium fluond>orate. This salt underwent slow solvolysis in a mixture of acetic acid — acetic anhydride with formation of the corresponding acetate. 

Acridine Yeiiow G (2,7-dimethylacridine-3,6-diamine hydrochloride)/775-49-9/ M 273.8, m 325 (free base). Cl 46025, pKj -3.0, pKl 0.5, pKl 8.9. Note that the hydrochloride is normally called Acridine Yellow G and not the free base. The free base recrystallises from 1 1 benzene/methanol, or from 800 parts of EtOH. It is converted to the sparingly soluble hydrochloride with dilute HCl, filtered off and dried. [Albert 7 Chem Soc 248 1947, Beilstein 22 IIEIV 5499,22/11 V 340.]... 

The 43 g. of basic mixture remaining after removal of the buphanamine was dissolved in 500 ml. of chloroform and shaken with 500 ml. of N hydrochloric acid. The chloroform layer was washed twice with water, and the aqueous solution was washed with chloroform. The combined aqueous solutions were neutralized carefully with concentrated sodium hydroxide (ice cooling) and made alkaline with excess potassium carbonate. Chloroform extraction of the basic solution gave 13.0 g. of free bases which formed water-soluble hydrochlorides. 

The chloroform layer containing the chloroform-soluble hydrochlorides was washed with concentrated potassium carbonate solution and dried over potassium carbonate. After removal of the chloroform under reduced pressure, there remained 30 g. of light brown, viscous oil which would not crystallize. The oil was dissolved in 250 ml. of 6% acetic acid cmd filtered through talc to remove traces of insoluble material. The warm... 

The 13 g. of alkaloids which formed water-soluble hydrochlorides was dissolved in... 

It should be mentioned that several more drastic simplifications of cocaine appeared on the scene even earlier. The only survivor is ethyl p-aminobenzoate (benzocaine, Table 13-6, No. 5). The others of interest were methyl p-amino-m-hydroxybenzoate (ortho-form), which, like benzocaine, was nontoxic, highly insoluble, and therefore not suitable for parenteral administration. Orthoform has no activity on intact skin, but it was useful as a powder on painful wounds. It was superseded commercially by the position isomer p-hydroxy-m-aminobenzoate methyl ester for reasons of cost since large-scale production of orthoform (as the pure, correct isomer) presented difficulties at the time. It should be pointed out that water-soluble hydrochlorides of the aminobenzoates can be prepared however, their solutions are much too acidic to inject. 

In agricultural application the water-soluble hydrochlorides are used in the case of both compounds for preventive soil treatment, seed dressing or for the preliminary soaking of the roots. 

Crystals from dil ale. mp 167°. Forms a water-soluble hydrochloride and sulfate. Used to form a repository form of penicillin G (as salt of benzylpenicillinic acid), trademarks Neopenyl, Lergopenin, DepocuraJ. Ref Arzneimittel-Fotsch. 4, 487 (1954). 

Octahedral crystals. Completely sol to a clear solu in 10% salt soln. Sol in di] mineral acids. Forms a water-soluble hydrochloride. 

Norlobelanidine, C21H27O2N. Lobelanidine is separated from the other Lobelia alkaloids by crystallization of its sparingly soluble hydrochloride (488), and the alcoholic mother liquors contain the hydrochloride of a secondary base. This base, which is optically inactive, melts at 120° and forms a hydrochloride, m.p. 244°, a nitrate, m.p. 179-180°, and a hydriodide, m.p. 211°. Since it is converted by methyl p-toluenesulfonate to lobelanidine and by oxidation with chromic acid to norlobelanine, the base is norlobelanidine. It is obtained as an intermediate product in the synthesis of lobelanidine (486). 

Bowdensine (CXXXIV R, Ri = CH3CO) and its 0,0-deacetyl derivative have been isolated from Nerine bowdenii (21). Bowdensine has not been isolated in crystalline form but is concentrated in the crude alkaloid fraction forming chloroform-soluble hydrochlorides. Bowdensine ([aJu + 17.3° in CHCI3) forms a methiodide (mp 284°-285° decomp. ... 

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