Diethylamine.hydrochloride

The experimental details describe the use of a free secondary amine for the preparation of a nitrosainine. Identical results are, of course, obtained by employing solid diethylamine hydrochloride. 

To this solution there is added in about 20 minutes a solution of diethylamine in CHCI3 while the temperature is kept below 35°C. The reacting mixture is heated to boiling, water formed during the reaction being distilled off thereby. After two hours the distillate contains no more water and the reaction is finished. Water is added to dissolve diethylamine hydrochloride formed during the reaction, and the chloroform layer containing the product is separated from the aqueous layer. The product may be purified by distillation it boils at 132°C at 0.2 mm pressure. It is converted to the citrate by reaction with citric acid. 

The reaction mixture warms slightly, resulting in the boiling of the ether. The large amount of diethylamine hydrochloride formed transforms the reaction mixture into a thick paste. 

The diethylamino homolog results when diethylamine hydrochloride is used. 

In a 3-1. round-bottomed flask equipped with a reflux condenser (Note 1) are placed 176 g. (1.60 moles) of diethylamine hydrochloride (Note 2), 68 g. (2.26 moles) of paraformaldehyde, 600 ml. (8.1 moles) of acetone, 80 ml. of methanol, and 0.2 ml. of concentrated hydrochloric acid. The mixture is heated for 12 hours at a moderate to vigorous rate of reflux (Note 3). The light-yellow solution, in which a small amount of gelatinous solid remains, is cooled, and a cold solution of 65 g. of sodium hydroxide in 300 ml. of water is added. The mixture is extracted with three 200-ml. portions of ether, the combined extracts are washed with two 150-ml. portions of saturated sodium chloride solution, and the washes are re-extracted with two 150-ml. portions of ether. 

A good grade of commercial diethylamine hydrochloride (Eastman Kodak white label or Matheson, Coleman and Bell) is satisfactory without purification. 

Diethylamine hydrochloride 1660-68-4J M 109.6, m 223.5°. crystd from dichloroethane/MeOH. Hygroscopic. 

As to N,N-dialkylhomologues of MDA, the N,N-dimethyl has been separately entered in the recipe for MDDM. Two efforts were made to prepare the N,N-diethyl homologue of MDA. The reasonable approach of reducing a mixture of diethylamine hydrochloride and 3,4-methylenedioxyphenylacetone in methanol with sodium cyanoborohydride was hopelessly slow and gave little product. The reversal of the functionality was successful. Treatment of MDA (as the amine) and an excess of acetaldehyde (as the carbonyl source) with sodium borohydride in a cooled acidic medium gave, after acid-base workup, a fluid oil that distilled at 85-90 °C at 0.15 mm/Hg and was converted in isopropanol with concentrated hydrochloric acid to 3,4-methylenedioxy-N,N-diethylamphetamine (MDDE) with amp of 177-178 °C. Anal. (C14H22ClNO,) N. 

Alkylquinoxalines undergo Mannich reaction with formaldehyde and diethylamine hydrochloride to afford diethylaminoethyl derivatives. ... 

Methylquinoxaline (7.2 g, 0.05 mol) was added to a mixture of diethylamine hydrochloride (7.7 g, 0.07 mol) and HCHO (10 mL). The mixture was refluxed and stirred for 20 h, and then diluted with H O (50 mL), treated with charcoal and filtered. The filtrate was extracted with EtjO (2 x 50 mL). The aqueous layer was basified by the addition of 10% aq NaOH (50-60 mL). The mixture was extracted with Et O (3 X 50 mL), the combined ethereal solutions dried (MgS04), treated with charcoal, filtered and the EljO evaporated. The residue was distilled at reduced pressure to give a yellow oil yield 3.6 g (31%) bp 168-172 C/9Torr. 

A solution of 200 g. (2.73 moles) of diethylamine in 150 ml. of ether is added slowly with intermittent cooling to 126 g. (1.37 moles) of chloroacetone. After the exothermic reaction has subsided, the mixture is heated under reflux for 5 hours. After cooling, the precipitated diethylamine hydrochloride is filtered off and the precipitate washed with ether. The combined filtrate and ether washings are distilled through a 15-cm. Vigreux column to give 127 g. (72%) of diethyl-aminoacetone boiling at 55-58 °/16 mm. 

A mixture of 22 g. (0.20 mole) of diethylamine hydrochloride, 60 ml. (0.82 mole) of acetone, 8.4 g. (0.28 mole) of paraformaldehyde, and 40 ml. of ethanol is refluxed on a steam bath for 20 hours. The resulting solution is filtered and concentrated by heating imder reduced pressure. To the concentrate are added 50 ml. of water and excess 45% aqueous potassium hydroxide solution. The resulting solution is saturated with potassium carbonate and extracted with ether. The ethereal solution is washed two times with saturated sodium chloride solution and dried over sodium sulfate and then over Drierite. Distillation from a modified Claisen flask gives 15.7-17.0 g. (55-59% yield) of the amino ketone boiling at 76-78°/16 mm. Analytically pure product is obtained by two redistillations, b.p. 70-70.5°/ll mm., 1.4333. 

The spectra of Fig. 3-21 present the remarkable structure of p, of solid diethylamine hydrochloride and hydrobromide. All of the features in the spectral region 1600-2500 cm" are iapparently associated with p Not a single feature in this richly structured band is lost on cooling the sample to 4°K. 

In the pyrazine series, the Mannich reaction was applied first to 2,5-dimethyl-pyrazine by Linder and Spoerri (715). Of the amines tried, positive reactions were obtained only with dime thy lamine, piperidine, and morpholine, and it was found that one, or more usually two, of the hydrogen atoms of each of the methyl groups could be substituted. Thus 2,5-dimethylpyrazine, dimethylamine hydrochloride, and formalin in refluxing isopentyl alcohol gave 2,5-bis[bis(dimethylaminomethyl)-methyl]pyrazine and 2,5-bis(j3-dimethylaminoethyl)pyrazine. Reaction of 2-methyl-pyrazine with formalin and diethylamine hydrochloride gave 2- 3-diethylamino-ethylpyrazine (716) similarly dimethylamine hydrochloride gave 2-dimethyl-aminoethylpyrazine (17) and some 2-[bis(dimethylaminomethyl)]methylpyrazine (18) (657). 

As dihydrocodeinone contains the system —CO—CH2— it was expected to undergo the Mannich reaction, and indeed after heating with dimethylamine hydrochloride and formaldehyde no dihydrocodeinone could be recovered, and only 40 per cent, of the product was crystalline. Under the same conditions 1-bromodihydrocodeinone (in which the reactive position of the aromatic nucleus is blocked, thus preventing any nuclear condensation) gave a 90 per cent, yield of crystalline material, also obtained when diethylamine hydrochloride was used in the reaction. The product cannot be sublimed, evidently boing dimolecular, and has been allotted the structure [lxvi, R = Br], i.e. 7 7 -methylenebis-(l-bromodihydrocodeinone). It is converted to 7 7 -methylenebis-(dihydrocodeinone) [lxvi, R = H] by catalytic reduction, and this is identical with the crystalline material obtained from dihydrocodeinone. A 5 5 or 5 7 -linkage is of course also possible, but the 7 7 union was considered to be most likely as it is the least hindered. No reaction occurs if triethylamine is substituted for the secondary amine, so that formation of a complex between the latter and... 

A vigorous reaction is observed between an ethereal solution of diethylamine and COCIF even at -78 C [589]. The product consisted of a mixture of diethylcarbamyl fluoride and diethylamine hydrochloride, which was separated by distillation ... 

Diethylamine hydrochloride [660-68-4] M 109.6, m 223.5", 226-229. Crystallise salt from absolute EtOH. Also crystallise it from dichloroethane/MeOH. Hygroscopic. [Beilstein 4111 113.]... 

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