Chloride Alkaloids

Ferric chloride Alkaloid skeletons by oxidative ring closure... 

Adrenaline and derivatives Alcohols, higher Aldehydes Alkali chlorides Alkaloids —, ergot —, hemlock —, veratrum —, vinca... 

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

Acetic Acid Acetic anhydride Acetoacetanilide Acetone cyanhydnn Acetyl chloride Acrolein Acrylonitrile Alcohols Alkaloids... 

Anderson first hydrolysed piperine by alkalis into a base and an acid, which were named by Babo and Keller piperidine and piperic acid respectively. The chemistry of these products is so well known that it need not be discussed here. The alkaloid was synthesised by Rugheimer by the action of piperoyl chloride on pijieridine. 

A comparison of the activities of these three alkaloids lias been made by Graliam and Gunn using their antagonism to the effects of carbamjd-choline chloride on isolated mammalian intestine. The relative activities found were, atropine sulphate 1 I-hyoscyamine sulphate 2-4 hyoscine hydro bromide 1-5. The results of previous authors are discussed and reasons suggested for some of the differences found. 

Laudanine, C20H25O4N, was isolated by Hesse. The crude alkaloid is purified by recrj stallisation from dilute alcohol for the removal of small quantities of cryptopine, or it may be dissolved in acetic acid and the solution poured into dilute caustic soda, when this impurity is precipitated and laudanine may be recovered from the filtrate by addition of ammonium chloride. It still contains its isomeride laudanidine, which may be separated by repeated crystallisation of the hydrochlorides, laudanidine accumulating in the aqueous mother liquors. The base crystallises from dilute alcohol, or from a mixture of alcohol and chloroform in rhombic prisms, m.p. 166°, [a]o 0°. It dissolves in solutions of alkali hydroxides, fornung metallic derivatives, which are precipitated by excess of alkali, but is nearly insoluble in solution of ammonia. The salts crystallise well ... 

Oxynarcotine, CjjHjaOgN. This alkaloid was separated by Mayer, and later by Beckett and Wright, from crude narceine. It crystallises from hot alcohol in small needles. Its close relationship to narcotine is shown by the formation of cotarnine, C12H15O4N (p. 201), and hemipinic acid when it is oxidised by ferric chloride narcotine under these circumstances furnishing cotarnine and opianic acid. Rabe and McMillan regard oxynarcotine and nomarceine as identical. 

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... 

The methochloride of (IX) occurs in two forms, identical with the a-and )S-forms of Modihydrocr3T)topine chloride (X). The two chlorides were converted into the two anhydrodihydrocryptopines A and B (p. 297). Of these the A base was oxidised by perbenzoic acid to the amine oxide (XI), m.p. 135° dec.), and this on heating with acetic and hydrochloric acids passed into cryptopine (XII), m.p. 220-1°, identical in all respects with the natural alkaloid. 

Worenine. This alkaloid, also obtained by Kitasato from Coptis japonica was isolated as the tetrahydro-base, C,oHjg04N, which crystallises from alcohol in colourless prisms, m.p. 212-3°, and is oxidised by iodine in alcohol to worenine iodide, yellow crystals from which worenine chloride, thin orange-yellow prisms, m.p. 295° (dec.), can be obtained. Tetrahydro-worenine behaves as a tertiary base, contains methylenedioxy- but no methoxyl groups, and its absorption spectrum closely resembles that of tetrahydrocoptisine from which it differs in empirical composition by. CHj. Worenine is, therefore, represented by (XXX), the alternative position (a) for the methyl group being untenable, since a-methyltetra-hydrocoptisine obtained by Freund s method is not identical with... 

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