Hydrogen chloride with ethers

By interaction of hydrogen cyanide and hydrogen chloride with an anxnatic compound (hydrocarbon, phenol or phenol ether) in the presence of aluminium chloride (or zinc chloride). This is known as the Gattermann... 

Treatment of a-thiocyanatoketones at low temperature with dry hydrogen chloride in ether solution gives satisfactory yields of 2-chloro-thiazole derivatives (188). The use of phosphorus pentachloride leads to the same results, but in this case chlorination can also occur at the 5-position (Scheme 97) (18, 68). 

Paraformaldehyde (7.5 g) (0.25 mol) and 18.3 g (0.25 mol) of diethylamine are mixed in 25 cc of alcohol and warmed until a clear solution Is obtained. The solution is cooled and mixed with 26.6 g (0.10 mol) of 3,3 -diallyl-4,4 -biphenol in 25 cc of alcohol. After standing several hours, the solution is warmed for one hour on the steam bath, allowing the alcohol to boil off. The residue is then taken up in ether and water, the ether layer separated and washed with 2% sodium hydroxide solution and finally with water. The washed ether solution is dried over solid potassium carbonate, and filtered. After acidifying with alcoholic hydrogen chloride, the ether is distilled off and the alcoholic residue diluted with an equal volume of acetone. The crystalline hydrochloride is filtered off, triturated with alcohol, diluted with several volumes of acetone, filtered and dried MP 209°-210°C. 

Preparation of Alkaloid Mixture 50 ml of the concentrated benzene solution, obtained as described was rapidly stirred, and a saturated solution of hydrogen chloride in ether added to the concentrated benzene solution until no more precipitate was obtained. The resulting precipitate was recovered by filtration and comprised the crude hydrochlorides of the extracted alkaloids and the hydrochloride of any unrecovered triethylamine. This material was dried by heating at a temperature of about 75°C for 6 hours, the crude, dried precipitate ground with 50 ml of isopropanol and to this slurry was added 1,000 ml of water. The resulting mixture was filtered. To the clear filtrate, cooled to 5°C, there was slowly added with rapid stirring, a 10% aqueous solution of ammonium hydroxide, until complete precipitation was accomplished. The precipitate was filtered off, washed with water and dried by heating at about 75°C for 6 hours. 

The basic ester may be dissolved in anhydrous ether and then precipitated by adding a slight excess of a solution of dry hydrogen chloride in ether and the hydrochloride salt may be isolated as an amorphous, glasslike product, which could be crystallized from anhydrous acetone or from methanol-ether. In this manner there was obtained as a stable, crystalline, colorless substance -dimethylaminoethoxyethyl phenothiazine-10-carboxylate hydrochloride, one sample of which melted at 161°-163°C with decomposition. 

Sodium methoxide (1.2 g) in dimethylformamide (150 ml) was stirred with 3,5-dim ethoxy-4 reaction mixture was then treated with /3-morpholinoethyl chloride (3.4 g) and heated for 1 hour at 140°C, then evaporated to dryness, and treated with water to give a solid material. The mixture was filtered, washed and crystallized from cyclohexane to give 3,5-di-methoxv-4 -chloro-4-( morpholinoethoxy)-benzophenone (6.5 g), MP 91°C to 92°C. The product was then reacted at about 0°C with gaseous hydrogen chloride in ether to give, after crystallization from isopropanol, the corresponding hydrochloride which hada MPof 187.9°C. 

Ethyl a-phenylacetoacetate can be prepared by the hydrolysis of a-phenylacetoacetonitrile in absolute alcohol with dry hydrogen chloride.1 The present method differs in specifying neutralization of the hydrogen chloride with sodium carbonate and hydrolysis of the imino ether in aqueous sulfuric acid, so that the product separates as fast as it forms, thus being protected from further decomposition, with a considerably increased yield as the result. 

Chloromethylnaphthalene has been made from naphthalene and a variety of reagents methyl chloromethyl ether 1 aqueous formaldehyde and hydrogen chloride with or without sulfuric... 

Maurer and Bohme62 reported that one mole of XIV, with acid chlorides in acid solution or with dry hydrogen chloride in ether, adds on halogen acid with the simultaneous production of two moles of benzoic acid per... 

Of the primary monoamines, some, such as. aniline, o-toluidine, xylidine, are colourless liquids. Others, such as p-toluidine, pseudo-cumidine and the naphthylamines, are solids. They can be distilled without decomposition and are volatile with steam. In water they are rather sparingly soluble—a 3 per cent solution of aniline can be made. The di- and polyamines are usually solids, not volatile in steam and much more soluble in water than the monoamines. The amines are basic in character, but, as a result of the negative nature of the phenyl-group, the aromatic amines are considerably weaker bases than are the aliphatic amines. Consequently aqueous solutions of the (stoicheio-metrically) neutral aniline salts are acid to litmus because of the hydrolysis which they undergo. For the same reason a small amount of the free base can be extracted with ether from an aqueous solution of an aniline salt. (Test with a solution of hydrogen chloride in ether or, after evaporation of the ether, by the reaction with bleaching powder.)... 

In a i-l. round-bottomed flask are placed 12 g. (0.5 gram atom) of magnesium powder, 37 g. (0.5 mole) of tert.-bvlyl alcohol, and 100 g. of anhydrous ether (Note 1). The flask is fitted with an addition tube, one arm of which bears a reflux condenser, and the other arm a dropping funnel. While the mixture is being shaken by hand, a solution of 55 g. (0.7 mole) of acetyl chloride (Note 2) in 50 g. of anhydrous ether is added dropwise (Note 3). A lively reaction gradually ensues with evolution of hydrogen, mixed with ether vapor and a little hydrogen chloride (Note 4). After all the acetyl chloride has been added, the reaction mixture is allowed to stand in a pan of cold water for one hour (Note 5). After another hour at room temperature the mixture is warmed in a water bath at 40-450 for one-half hour in order to complete the reaction. 

The complex hydride reductions of nitriles to aldehydes compare favorably with the classical Stephen reduction which consists of treatment of a nitrile with anhydrous stannous chloride and gaseous hydrogen chloride in ether or diethylene glycol and applies to both aliphatic and aromatic nitriles [183,285, 1152]. An advantage of the Stephen method is its applicability to polyfunctional compounds containing reducible groups such as carbonyl that is reduced by hydrides but not by stannous chloride [1153]. 

The A-methyl-A -arylazoaminoacetonitriles (194) and hydrogen chloride in ether yield the 1,2,3-triazolium chlorides (195). These salts (195) and base did not give the corresponding meso-ionic compounds (193, R = Me, R == Ar, R = R = H), but the corresponding J acetyl derivatives (193, R = Me, R = Ar, R = H, R = Ac) were produced either from the nitriles (194) and acetyl chloride or from the 1,2,3-triazolium chlorides (195) and acetic aidiydride, followed by treatment with ammonium hydroxide. ... 

Passage of hydrogen chloride into ether solutions of 76 and Ai-oxides 94-9765.79 results similarly in protonation and hydration. Thus, for example, 95 gives 140, convertible back to 95 with base likewise, among other examples, 94 is converted to 141 in ethanol. ... 

Selective demethylation of 2,4-dimethoxyquinolines occurs on heating with hydrogen chloride in ether, normally giving 4-methoxyquinol-2-ones, e.g. Scheme 103 <73JCS(Pl)94). If, however, alkali is used and an electron-withdrawing 3-substituent is present, as in (118), then the demethylation occurs at position 4 (Scheme 103) <8iiJC(B)543). 

The possibility of selective hydrolysis of one of the imino ether functions in the bislactim ether has been discussed by Schollkopf (88LA1025). This procedure if accomplished regiospecifically would be extremely useful. Treatment of the bislactim ether with one equivalent of hydrogen chloride in ether does give rise to a monolactam monolactim ether however, the state of the art at present does not give control over the regioselectivity. 

Chlorothexylborane (1). Mol. wt. 132.44. One synthesis involves the reaction of thexylborane with 1 equivalent of hydrogen chloride in ether.1 This reagent can also be prepared by reaction of 2,3-dimethyl-2-butene with monochloroborane -dimethyl sulfide (equation I).2... 

There is an interesting difference in the cydization of the closely related pyrrole derivatives 7 and 9. A reaction of N-vinylpyrrole 7 with hydrogen chloride in ether yielded a dark blue immonium salt, represented by resonance structures 8a and 8b. The N-ethyl analog (9), on the other hand, gave the 1-amino-3//-pyrrolizine (10) under the same conditions. Hydrolysis of 8 did not give the expected pyrrolizinone(12) but stopped half way to give adduct 11.19... 

Ethers are formed in the usual way the te-chloromethyl ether is obtained by using formaldehyde and hydrogen chloride. With aldehydes or their derivatives, butanediol forms acetals, either 7-membered rings (1,3-dioxepanes) or linear polyacetals the rings and chains are easily intraconverted. 

The treatment of KBeHn with hydrogen chloride in ether solution 17 8) produces BeHi2 in yields which are low but comparable to the presently preferred method of preparation 168). 

Brown et al. achieved a highly enantioselective synthesis of (.S )-fluoxetine hydrochloride (61) (Prozac), an antidepressant medicine26 (Scheme 4.3v). Reduction of (3-chloropropiophenone (62) with (+)-Ipc2BCl provided the secondary alcohol 63 in 97% ee and greater than 99% ee after single recrystallization. Mit-sunobu reaction of the alcohol with p-trifluoromethylphenol afforded the ether 64, which was then converted to (S)-(+)-fluoxetine hydrochloride (61) after subsequent treatment with excess methylamine and a solution of hydrogen chloride in ether. 

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