Hydrochloric acid reactions with alcohol

Dissolve 1 g. of the secondary amine in 3-5 ml. of dilute hydrochloric acid or of alcohol (in the latter case, add 1 ml. of concentrated hydrochloric acid). Cool to about 5° and add 4-5 ml. of 10 per cent, sodium nitrite solution, and allow to stand for 5 minutes. Add 10 ml. of water, transfer to a small separatory funnel and extract the oil with about 20 ml. of ether. Wash the ethereal extract successively with water, dilute sodium hydroxide solution and water. Remove the ether on a previously warmed water bath no flames should be present in the vicinity. Apply Liebermann s nitroso reaction to the residual oil or solid thus. Place 1 drop or 0 01-0 02 g. of the nitroso compovmd in a dry test-tube, add 0 05 g. of phenol and warm together for 20 seconds cool, and add 1 ml. of concentrated sulphuric acid. An intense green (or greenish-blue) colouration will be developed, which changes to pale red upon pouring into 30-50 ml. of cold water the colour becomes deep blue or green upon adding excess of sodium hydroxide solution. 

Hydroisoquinolines. In addition to the ring-closure reactions previously cited, a variety of reduction methods are available for the synthesis of these important ring systems. Lithium aluminum hydride or sodium in Hquid ammonia convert isoquinoline to 1,2-dihydroisoquinoline (175). Further reduction of this intermediate or reduction of isoquinoline with tin and hydrochloric acid, sodium and alcohol, or catalyticaHy using platinum produces... 

Terpineol nitrosochloride, Cj Hj-OH. NOCl, is, perhaps, the most suitable derivative to prepare for the identification of terpineol. To a solution of 15 grams of terpineol in 15 c.c. of glacial acetic acid, 11 c.c. of ethyl nitrite are added. The mixture is cooled in ice, and 6 c.c. of hydrochloric acid mixed with 6 c.c. of glacial acetic acid are added drop by drop, with continual shaking. Care must be taken to avoid a rise in temperature. When the reaction is compdete, water is added to pjre-cipitate the nitrosochloride. The oily liquid soon solidifies and may be recrystallised from boiling acetic ether or from methyl alcohol. Ter-... 

The pH is adjusted to 5.5 and the water phase separated and extracted with additional ether in order to remove the surplus dimethyl anilin. After addition of an excess of ammonia to the solution, the reaction product, N-methylpipecolic acid 2,6-dimethyl anilide, is recovered by extraction with isoamyl alcohol. The isoamyl alcohol solution is evaporated to dryness, the product dissolved in dilute hydrochloric acid, treated with charcoal and reprecipitated with NaOH. N-methylpipecolic acid 2,6-dimethyl anilide is obtained in crystalline form. 

Grignard gives the tertiary alcohol after hydrolysis. Reaction of the alcohol with hydrochloric acid proceeds with rearrangement and opening of the strained cyclopropane to give a chloride. Sn2 displacement of the chloride with dimethylamine forms amitriptyline. Alternatively, dibenzosuberone can be reacted with dimethylaminopropyl Grignard to form an alcohol, which upon dehydration forms amitriptyline. 

Method I.—7 gms. (1 mol.) of finely powdered potassium cyanide and 14 gms. (1 mol.) of finely powdered anthranilic acid are suspended in 50 c.cs. of ether or benzene in a flask fitted with a reflux condenser. The whole is well cooled in a freezing mixture, and 7 5 c.cs. (1 mol. CH20) of 40% formalin are slowly added. A brisk reaction sets in, and two layers are formed, the lower of which solidifies on cooling to a mass of crystals of the potassium salt of the required acid. This is collected, dissolved in water, the free acid precipitated by acidification with acetic or hydrochloric acid, washed with cold water, and recrystallised from alcohol, benzene, or chloroform. 

Add 8.0g (10.0ml, 0.15 mol) of redistilled acrylonitrile (Expt 5.161, Note (1)) to a stirred solution of diethyl propylmalonate (30.2 g, 0.15 mol) (Expt 5.132) and of 30 per cent methanolic potassium hydroxide (4.0 g) in t-butyl alcohol (100 g). Keep the reaction mixture at 30-35 °C during the addition and stir for a further 3 hours. Neutralise the solution with 2 M-hydrochloric acid, dilute with water and extract with ether. Dry the ethereal extract with anhydrous sojdium sulphate and distil off the ether the residue [diethyl (2-cyanoethyl)-propylmalonate 11 g] solidifies on cooling in ice, and melts at 31—32 °C after recrystallisation from ice-cold ethanol. Boil the cyanoethyl ester (10 g) under reflux with 40 ml of 48 per cent hydrobromic acid solution for 8 hours, and evaporate the solution almost to dryness under reduced pressure. Add sufficient water to dissolve the ammonium bromide, extract several times with ether, dry the ethereal extract and distil off the solvent. The residual oil (4.5 g, 66%) soon solidifies upon recrystallisation from water, pure 2-propylglutaric acid, m.p. 70 °C, is obtained. 

To a solution of 100 g. (2.0 moles) of 98 per cent sodium cyanide in 400 cc. of water, contained in a 3-1. round-bottomed llask fitted with a Hershberg stirrer (Org. Syn. 17, 31), is added IIX g. (2.2 moles) of ammonium chloride. The mixture is stirred at room temperature under a properly ventilated hood. When the ammonium chloride has dissolved, a solution of 212 g. (2.0 moles) of benzaldehyde in 400 cc. methyl alcohol is added in one portion. The reaction begins rapidly, the temperature rising to about 45°. Stirring is continued for two hours. The heterogeneous mixture, after dilution with 1 1. of water, is extracted with 1 1. of benzene, and the aqueous layer is discarded. The benzene layer is washed with three 50-cc. portions of water, and I lie aminonitrile is extracted, in the form of its hydrochloride, by shaking the benzene solution with 6 N hydrochloric acid, first with one 600-ce. portion and then with two 300-cc. portions. 

Violent reaction with alcohols, N-aryl sulfinamides, dimethyl formamide, polychlorobiphenyl, sodium hydroxide, hydrochloric acid + dinitroanilines. Incandescent reaction when warmed with cesium oxide (above 150°), tellurium, arsenic, tungsten dioxide. Potentially dangerous reaction with hydrocarbons + Lewis acids releases toxic and reactive HCl gas. 

SAFETY PROFILE A highly corrosive irritant to the eyes, skin, and mucous membranes. Mildly toxic by inhalation, Explosive reaction with alcohols + hydrogen cyanide, potassium permanganate, sodium (with aqueous HCl), tetraselenium tetranitride. Ignition on contact with aluminum-titanium alloys (with HCl vapor), fluorine, hexa-lithium disilicide, metal acetylides or carbides (e.g., cesium acetylide, rubidium ace-tylide). Violent reaction with 1,1-difluoro-ethylene. Vigorous reaction with aluminum, chlorine + dinitroanilines (evolves gas). Potentially dangerous reaction with sulfuric acid releases HCl gas. Adsorption of the acid onto silicon dioxide is exothermic. See also HYDROGEN CHLORIDE (AEROSOL) and HYDROCHLORIC ACID. 

Fifteen grams of crude diisonitrosoacetone is added in small portions over a 1-hour period to a mixture of 110 ml. of concentrated hydrochloric acid and 400 g. of stannous chloride. The temperature of the reaction mixture is held to 20-30° by occasional cooling. Another 110 ml. of concentrated hydrochloric acid is added, and this is followed by the addition of another 18 g. of diisonitrosoacetone in the same manner as before. Another 50 ml. of concentrated hydrochloric acid is added, and the mixture is cooled in the refrigerator overnight. The mixture is then filtered by suction, and the precipitate is washed with concentrated hydrochloric acid followed by alcohol. The resulting dry stannous chloride salt of diaminoacetone weighs 80-87 g., which corresponds to an 80-85%i yield. 

This derivative is isolated in the form of its dihydrochloride when a mixture of 3 3 - diamino-5 5 - diacetamido -4 4 - dihydroxyarseno-benzene and 3 3 -diamino-4 4 -dihydroxyarsenobenzene in a common solvent is treated with an excess of methyl alcoholic hydrochloric acid or with ether. The reaction is an example of the general reaction indicated by the following equation ... 

I) Isocyanide Reaction of Primary Amines. Place 1 drop of aniline in one test tube, and 1 drop of n butylamine in another. Add to each 3 or 4 drops of chloroform and 1 ml of alcoholic potash. Use the hood.) Warm it for a few seconds. The isocyanides can be recognized by the odor. Clean the tube with concentrated hydrochloric acid, then with water. Write the equation for the reaction. What is the structure of isocyanide ... 

---