3-Dimethylaminoethyl chloride, reaction

Cationic Starches. The two general categories of commercial cationic starches are tertiary and quaternary aminoalkyl ethers. Tertiary aminoalkyl ethers are prepared by treating an alkaline starch dispersion with a tertiary amine containing a P-halogenated alkyl, 3-chloto-2-hydtoxyptopyl radical, or a 2,3-epoxypropyl group. Under these reaction conditions, starch ethers are formed that contain tertiary amine free bases. Treatment with acid easily produces the cationic form. Amines used in this reaction include 2-dimethylaminoethyl chloride, 2-diethylaminoethyl chloride, and A/-(2,3-epoxypropyl) diethylamine. Commercial preparation of low DS derivatives employ reaction times of 6—12 h at 40—45°C for complete reaction. The final product is filtered, washed, and dried. 

An alternate scheme for preparation of the last drug involves first bromination of the methylene group on 33 (obtainable by several methods from 27). A displacement reaction of the Grignard reagent prepared from 34 on 2-dimethylaminoethyl chloride affords again amytriptylene (32). ... 

The low structural specificity of the antihistamines has already been noted. It is perhaps not too surprising, therefore, to find Lhat attachment of the basic side chain directly onto one of the. iromatic rings affords active compounds. In an unusual reaction reminiscent of the Claisen rearrangement, benzyl chloride affords the substituted phenol, 46, on heating with phenol itself. Alkyl-.ition of 46 with 2-dimethylaminoethyl chloride gives phenyltolox-.imine (47).Alkylation of that same intermediate (46) with 1-bromo-2-chloropropane, leads to 48. Use of that halide to alkyl-,ite piperidine gives the antihistamine, pirexyl (49). ... 

According to US Patent 2,676,964 to 1.0 mol of potassium amide in 3 liters of liquid ammonia, is added 1.0 mol of 2-benzylpyridine. After 15 minutes, 1.1 mols of fS-dimethylaminoethyl chloride are added. The ammonia is allowed to evaporate and the reaction product decomposed with water and ether extracted. The ether layer is dried over sodium sulfate and after evaporation the residue is distilled, giving the 3-phenyl-3-(2-pyridyl)-N,N-dimethylpropylamine, BP 139°-142°C/l-2 mm. The maleate is produced by reaction with maleic acid. 

A suspension of 30 g of sodium hydride in benzene (30 ml) was added dropwise to 52 g of 8-chlorodibenzo[b,f]thiepin-10(llH)-one dissolved in dimethylformamide (800 ml), and the mixture was heated at 100°C for 2 hours. To this, there were added 68 g of 2-dimethylaminoethyl chloride, and the mixture was heated at 60°C for 39 hours. The reaction mixture, after cooled, was poured into ice-water, and the solution was extracted with ethyl acetate. The ethyl acetate layer, after washed with water, was extracted with 10% hydrochloric acid, when oil was precipitated. The aqueous layer, in which oil was precipitated, was washed with ether, made neutral with concentrated sodium hydroxide solution and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over magnesium sulfate, and concentrated to give oil, which was allowed to stand to provide solid. The solid was washed with petroleum ether and recrystallized from cyclohexane to yield 42.5 g of 8-chloro-10-(2-dimethylaminoethyl)-oxydibenzo[b,f]thiepin as crystals, melting point 90°C to 91°C. Maleate as colorless needle, melting point 204°C to 204.5°C. 

A related noncatalytic alkylation of the nitrogen atom is shown by the following reaction of benzylphenylamine with /3-dimethylaminoethyl chloride in the presence of lithium amide to yield N-benzyl-N-phenyl-N, N -dimethyl-l,2-diam-inoethane ... 

To a solution of previously dried l-[[2-carboxy-3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]-pyrrolidine (1.6 g 0.0442 moles) in anhydrous quinoline (75 ml) and under atmosphere of nitrogen, cuprous oxide (160 mg 0.0011 moles) was added. The reaction mixture was heated to 190°C for 15 minutes, stirred to room temperature, poured into a mixture of 1 N hydrochloric acid (150 ml) and ethyl acetate (50 ml), shaken and decanted. The aqueous solution was washed several times with ethyl acetate, then solid sodium bicarbonate was added until pH = 7.8, and washed with n-hexane to eliminate the quinoline. The aqueous solution was made alkaline with solid potassium carbonate and extracted with ethyl acetate. The organic solution was dried (Na2S04), the solvent removed under reduced pressure when a dark oil was obtained (1.3 g yield 92%). This product was purified by column chromatography with silica gel and methylene chloride ethanol ammonium hydroxide (60 8 1) as eluent and a white foam (0.8 g) of l-[[3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]-pyrrolidine was obtained. To a solution of the above product (0.8 g) in acetone (30 ml), a few drops of hydrogen chloride saturated dioxan solution, were added. The precipitated solid was collected by filtration, washed with acetone and dried to give l-[(3-(2-(dimethylamino)ethyl)-5-indolyl)methanesulphonyl]-pyrrolidine hydrochloride (0.75 g). Melting point 218°-220°C. 

A solution of 21.7 g (0.11 mole) 1-adamantanecarboxylic acid chloride in 100 ml ether was added to a solution of 19.4 g (0.22 mole) 2-dimethylaminoethanol in 200 ml ether. The reaction mixture was stirred overnight at room temperature. Then additional 15.0 g (0.17 mole) 2-dimethylaminoethanol was added and the reaction mixture again stirred overnight. The reaction mixture was poured into 300 ml water and treated with 20 ml of 10% NaOH solution. From the ether layer was recovered 23.0 g of 2-dimethylaminoethyl 1-adamantanecarboxylate as oil. 

Initially, 4-bromobenzyl-cyanide is reacted with sodium amide and 2-chloropyridine to give bromophenyl-pyridyl acetonitrile. This is then reacted with sodium amide then dimethyl amino ethyl chloride to give 4-bromophenyl-dimethylaminoethyl-pyridyl acetonitrile. This intermediate is then hydrolyzed and decarboxylated to bromphenirame using 80% H2S04 at 140°-150°C for 24 hours. The brompheniramine maleate may be made by reaction with maleic acid in ethanol followed by recrystallization from pentanol. 

In an alternative procedure to autoxidation, mesitylene iodosoacetate has been used for the oxidation of 2-dimethylaminoethyl 2,5-dimethylphenyl ether to 2-dimethylaminoethyl 4-hydroxy-2,5-dimethylphenyl ether (ref48). The starting phenol in acetic anhydride containing mesitylene iodosoacetate was treated slowly below 10°C with sulphuric add and after a reaction time of approximately 18 hours the mixture was quenched at with water and, following a work-up involving addition of ether and cuprous chloride, the product was isolated in 61 % yield. 

VInylpyrrolldone/dImethylaminoethyl methacrylate copolymer/diethyl sulfate reaction product. SeePolyquaternium-11 Vinyl pyrrolidone homopolymer. See PVP Vinylpyrrolidone/methacrylamidopropyltrimethy I ammonium chloride copolymer. See Polyquaternium-28... 

By essentially the same procedure antipyrine and Intercain (dimethylaminoethyl ester of /)-butyIaminobenzoic acid hydro-chloride)< > were determined. The attack by nitrous acid is probably on the phenyl ring, but the reaction products, which show a polarographic reduction wave, were not identified. 

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