Alkaloidal solubilities

All the possible degrees of acidity or alkalinity are found in the range between zero and fourteen on the pH scale. This is crucial for us to know, since it is a fact of nature that to make alkaloids soluble in water we must first make them acidic. Conversely, for them to be soluble in an organic solvent, such as ether, we must make them basic or alkaline. Most of the psychoactive substances we are interested in extracting are called "alkaloids," compounds numerically above 7 in pH. Webster s Third New international Dictionary defines the word for us ... 

In the commercial extraction of alkaloids from the drugs in which they exist, the powdered drug, or an alcoholic extract of it, is treated with an alkali such as ammonia or lime to liberate the alkaloid and the alkaloid is then extracted by means of an organic solvent. The crude material thus obtained is purified and finally crystallized either as the base itself or as its water-soluble salts. 

Although their presentiy accepted stmctures were unknown, they were characterized with the tools available at the time. Because morphine (2, R = H), C22H22NO 3, was shown to have properties similar to the basic soluble salts obtained from the ashes of plants (alkah) it was categorized as a vegetable alkaU or alkaloid, and it is generally accepted that it was for this case the word was coined. 

Both of the alkaloids anhalamine (62) from l ophophora williamsii and lophocerine (63) from l ophocereus schotti were isolated (after the properties of purified mescaline had been noted) in the search for materials of similar behavior. Interestingly, lophocerine, isolated as its methyl ether, after dia2omethane treatment of the alkaU-soluble fraction of total plant extract, is racemic. It is not known if the alkaloid in the plant is also racemic or if the isolation procedure causes racemization. 

Rya.nia., The root and stem of the plant yania speciosa family Flacourtiaceae, native to South America, contain from 0.16—0.2% of iasecticidal components, the most important of which is the alkaloid ryanodine [15662-33-9] C25H250 N (8) (mp 219—220°C). This compound is effective as both a contact and a stomach poison. Ryanodine is soluble ia water, methyl alcohol, and most organic solvents but not ia petroleum oils. It is more stable to the action of air and light than pyrethmm or rotenone and has considerable residual action. Ryania has an oral LD q to the rat of 750 mg/kg. The material has shown considerable promise ia the control of the European com borer and codling moth and is used as a wettable powder of ground stems or as a methanohc extract. Ryanodine uncouples the ATP—ADP actomyosia cycle of striated muscle. 

Acetylcholine. Acetylcholiae (ACh) (1) is a crystalliae material that is very soluble ia water and alcohol. ACh, synthesized by the enzyme choline acetyltransferase (3), iateracts with two main classes of receptor ia mammals muscarinic (mAChR), defiaed oa the basis of the agonist activity of the alkaloid muscarine (4), and nicotinic (nAChR), based on the agonist activity of nicotine (5) (Table 1). m AChRs are GPCRs (21) n AChRs are LGICs (22). 

The slightly soluble ion pair was used as electrode-active substance in a plastered membrane of an ion-selective electrode (ISE) for these alkaloids. 

Conhydrine, CgHj, ON. This oxygenated alkaloid was isolated by Wertheim. It crystallises in colourless leaflets, has a coniine-like odour, can be sublimed and is strongly basic, m.p. 121°, b.p. 226°, Wd 4" 10°- It is soluble in alcohol or chloroform, moderately so in water and in ether, from which it crystallises readily. The salts are crystalline the aurichloride small rhombs or pri.sims, m.p. 133° the benzoyl derivative m.p. 132°. 

The alkaloid may be separated from accompanying hyoscyamine by extracting most of it with ether and then crystallising the mixed oxalates from water, that of norhyoscyamine separating first. It crystallises in colourless prisms, m.p. 140°, [a]j, — 23-0° (50 per cent. EtOH), is soluble in alcohol or chloroform, less so in ether or acetone, and sparingly in water... 

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. ... 

Karrer and Schmid have examined the water-soluble constituents in poppy straw after extraction of the alkaloids, and have recorded the presence of -hydroxybenzaldehyde, vanillin, -hydroxystyrene, meconin and the following acids fumaric, dZ-lactic, benzoic, -hydroxycinnamic, p-hydroxybenzoic, 2-hydroxycinchoninic, vanillic, phthalic, hemipinic and m-hemipinic, with a more highly unsaturated, carboxylic acid J, b.p. 170-570-02 mm., and three unidentified substances Fa , m.p. 271-2° Wx, m.p. 310° (dec.) and Q, m.p. 260° the two latter are free from nitrogen and contain no methoxyl. 

Papaverine crystallises in rhombic prisms or needles, m.p. 147°, [a]n 0°, is insoluble in water, soluble in hot alcohol or chloroform, and slightly so in cold alcohol or ether. It is a weak base for which, according to Wales, there is no satisfactory indicator, though bromophenol-blue has its colour change at the right point for this alkaloid. The hydrochloride, B. HCl, forms monoclinic plates, m.p. 225-6°, sparingly soluble in water (1 in 37 at 18°). The picrate forms quadratic plates, m.p. 186°. ... 

Laudanosine, C21H27O4N. This alkaloid occurs in the liquor from which thebaine is precipitated, and can be isolated by Hesse s method. The crude alkaloid is purified by extraction with small quantities of ether, in which laudanosine is soluble, and finally by precipitation with potassium iodide. The free base crystallises from hot benzene in needles, m.p. 89°, [ ] f 103-23° (EtOH), is soluble in alcohol, chloroform, hot benzene or... 

Meconidine, C21H23O4N. This alkaloid was prepared by Hesse and its existence in Japanese opium was confirmed by Machiguchi. It is a brownish-yellow, amorphous substance, m.p. 58°, easily soluble in alcobol, most organic solvents and in alkalis. It gives a green solution with sulphuric acid. The salts are amorphous. Meconidine is said to exhibit a slight tetanising action. 

---