I Methyl alcohol

Triazolam, USP. Triazolam. 8-chloro-6-(o-chlorophc-nyl)-l-methyl-4Ay-j-triaz.olol4.3-a f l,4 benzxxliazcpinc (Hal-cion). has all of the characteristic benzodiazepine pharmacological actions. It is marketed as a sedative-hypnotic drug said to impair little, if any. daytime function. It is rapidly metabolized to the I-methyl alcohol, which is then conjugated and excreted. 

Equip a 500 ml. three-necked flask with an efficient stirrer (e.g., a Hershberg stirrer. Fig. II, 7, 8) and a reflux condenser stopper the third neck. Place a solution of 30 g. of sodium hydroxide in 100 ml. of water, and also 20-5 g. (17-1 ml.) of pure nitrobenzene in the flask, immerse it in a water bath maintained at 55-60°, and add 21 g. of anhydrous dextrose in small portions, with continuous stirring, during 1 hour. Then heat on a boiUng water bath for 2 hours. Pour the hot mixture into a 1 litre round-bottomed flask and steam distil (Fig. II, 40, 1) to remove aniline and nitrobenzene. When the distillate is clear (i.e., after about 1 htre has been collected), pour the residue into a beaker cooled in an ice bath. The azoxybenzene soon sohdifies. Filter with suction, grind the lumps of azoxybenzene in a mortar, wash with water, and dry upon filter paper or upon a porous plate. The yield of material, m.p. 35-35-5°, is 13 g. Recrystallise from 7 ml. of rectified spirit or of methyl alcohol the m.p. is raised to 36°. ... 

For my part, although I may be somewhat of a visionary, I see a solution to the problem by chemical recycling of excess carbon dioxide emissions into methyl alcohol and derived hydrocarbon products. 

The mother liquor and washings are returned to the flask and again boiled for seventy-two hours under reflux. The liquid is concentrated to 8oo cc. and again chilled to 0°, inoculated and allowed to stand at 0° for twenty-four hours. The second crop of glucoside so obtained is filtered by suction and washed with three loo-cc. portions of cold methyl alcohol. This yield is no-145 g-i nielting at i64-r65°. The mother liquor and washings are combined and concentrated to about 300 cc., chilled to 0°,... 

Technical formalin contains 8-10 per cent of methyl alcohol, so that it is not possible to use the table of densities (Note i of the preparation) for determining the formaldehyde content of the solutions. For example, a solution containing 37 per cent of formaldehyde and 10 per cent of methyl alcohol would have a density of 1.09 and correspond to 28 per cent of formaldehyde in pure water. In view of this, the recorded yield should probably be 64-66 per cent instead of 86-89 cent. 

The most common impurities are the corresponding acid and hydroxy compound (i.e. alcohol or phenol), and water. A liquid ester from a carboxylic acid is washed with 2N sodium carbonate or sodium hydroxide to remove acid material, then shaken with calcium chloride to remove ethyl or methyl alcohols (if it is a methyl or ethyl ester). It is dried with potassium carbonate or magnesium sulfate, and distilled. Fractional distillation then removes residual traces of hydroxy compounds. This method does not apply to esters of inorganic acids (e.g. dimethyl sulfate) which are more readily hydrolysed in aqueous solution when heat is generated in the neutralisation of the excess acid. In such cases, several fractional distillations, preferably under vacuum, are usually sufficient. 

Cellobiose was prepared first by Skraup and Konig by the saponification of the octaacetate with alcoholic potassium hydroxide, and the method was improved by Pringsheim and Merkatz.3 Aqueous barium hydroxide also has been employed for the purpose, and methyl alcoholic ammonia has been used extensively for the hydrolysis of carbohydrate acetates. The method of catalytic hydrolysis with a small quantity of sodium methylate was introduced by Zemplen,i who considered the action to be due to the addition of the reagent to the ester-carbonyl groups of the sugar acetate and the decomposition of the addition compound by reaction with alcohol. The present procedure, reported by Zemplen, Gerecs, and Hadacsy, is a considerable improvement over the original method (see Note 2). 

Willstatter and Bode converted tropinone into (/(-ecgonine by treating sodium tropinone with carbon dioxide and sodium, when it yielded sodium tropinonecarboxylate. This on reduction with sodium in alcohol gave some dZ-i/i-ecgonine (p. 97), which on esterification with methyl alcohol and benzoylation yielded a dhcocainc. A simpler synthesis of ( -eegonine was achieved by Willstatter and Bommer, and reference is made on p, 80 to this and other processes, some of which have been protected by patents. These improvements having enabled the prepara-... 

In like manner lodal (VI), on condensation with 6-nitro-3 4-methylene-dioxyphthalide (IV) yields nitro-a -adlumine (I R = NOj . O. CHa. O. at C and C replaced by 20Me), which crystallises from chloroform-methyl alcohol in orange, rectangular plates, m.p. 180-1° dec.), and on reduction yields the corresponding amino-derivative, bundles of minute needles, m.p. 218-9°. 

Thebainol (Pschorr Dihydrometathebainone (Schopf i), CigHjgOjN, is obtained by the reduction of metothebainone, with sodium amalgam in dilute alkali. Crystallised from methyl alcohol, it melts at 54-5° and re-melts at 76-8°, but after crystallisation from dry ether it has m.p. 135-6° and [a]f ° + 67-05° (EtOH). The oxime has m.p. 217-8° and [a][, ° + 104-2° (acetic acid, 10%). The benzylidene derivative forms yellow needles, m.p. 100-2°. An amorphous dipiperonylidene derivative has been described by Gulland and Robinson.The methyl ether is amorphous, but yields a crystalline methiodide, m.p. 245°. Thebainol is represented as (L), produced by saturation of the ethylenic (C -C ) linkage in meta-thebainone (LII). 

This formula was confirmed hy Haworth and Perkin s synthesis of a-flZZocryptopine from herherine, the first application of a process, of which examples have heen given already in the syntheses of cryptopine (p. 298) and protopine (p. 301) hy the same authors. Anhydrotetrahydromethyl-herherine (I cf. hase (a), p. 346) in dry chloroform was added to a solution of perhenzoic acid in ether cooled helow 5°. The amine oxide, C21H23O5N (II), separated as an oil, which after shaking with sodium hydroxide solution, solidified and was crystallised from water in slender prisms, m.p. 135°. It was dissolved in acetic acid, hydrochloric acid added, the mixture heated in boiling water for an hour and the hase precipitated hy addition of potassium hydroxide. The precipitate was dissolved in methyl alcohol, ether added, the alcohol washed out with water and the ethereal... 

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