Glycine ethyl ester.hydrochloride

In a 3-I. round-bottomed flask are placed 500 cc. (400 g., 8.7 moles) of absolute alcohol which has been saturated in the cold with hydrochloric acid gas (Note i), 870 cc. (6S0 g., 20 moles) of 96 per cent alcohol (Note 2) and 70 g. (1.03 moles) of methyleneaminoacetonitrile (Note 3). This mixture is refluxed on a steam bath for three hours (Note 4). During the refluxing, ammonium chloride separates. After the reaction is complete, the hot alcohol solution is filtered with suction and the filtrate cooled, thus allowing the glycine ester hydrochloride to separate out in fine white needles. The product is filtered with suction, sucked as dry as possible on the filter, and then allowed to dry in the air. The yield is about no g. The alcohol from the filtrate is distilled (Note 5) until about one-third of its volume is left and again cooled and a second crop of crystals is obtained. The total yield of product, m.p. 142-143, varies from 125 to 129 g. (89-91 per cent of the theoretical amount). If a very pure product is desired, it may be recrystallized from absolute alcohol. 

The 500 cc. of absolute alcohol is cooled in an ice bath and treated with dry hydrogen chloride until 163 g. has been added, an amount sufficient for saturation. The solution should be protected from the moisture of the air with a calcium chloride tube. 

A cork and not a rubber stopper should be used during the refluxing, as rubber stoppers will cause the product to be colored. 

Care must be taken that no water gets into the alcohol, as glycine ester hydrochloride is quite soluble in water. Concentration of the filtrate on the steam bath should not be carried out in an open vessel because the solution will take up moisture and the product will not crystallize. 

Glycine ethyl ester hydrochloride has been prepared by the action of absolute alcohol and hydrogen chloride on glycine from glycyl chloride and alcohol by the action of ammonia or hexamethylenetetramine on chloroacetic acid, and subsequent hydrolysis with alcoholic hydrochloric acid and by the action of hydrogen chloride and alcohol on methyleneamino-acetonitrile.  

2 A few grammes of the salt mixture are laid aside for the preparation of hippuric acid as desoribed below. 

In addition to this, the simplest method of synthesising a-amino-acids (a method which is less satisfactory for the preparation of higher members of the series), there are two other processes, both starting from aldehydes. Strecker obtained the nitrile of the amino-acid, Chap. V. 7, p. 229, by addition of ammonium cyanide to the next lower aldehyde, and Erlenmeyer jun. condensed hippuric acid with the aldehyde containing two carbon atoms less than the required amino-acid. 

Ih this latter process an a/3-unsaturated a-benzoylamino-acid is formed and is converted into the a-amino-acid by hydrogenation and subsequent removal of the benzoyl group by hydrolysis. 

Recall the importance of the amino-acids as units from which the proteins are built up. What amino-adds have hitherto been isolated from proteins by digestion and by acid hydrolysis  

By the method of E. Fischer it is possible to carry out a separation, in some degree quantitative, of the individual a-amino-acids. They are esterified as described above, and the esters are then separated from one another by fractional distillation of the mixture in vacuo. 

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N-Benzoyl L-leucylglyclne ethyl ester (3). N-Benzoy-L-leucine 1 (0.235 g, 1 mmol) and glycine ethyl ester hydrochloride 2 (0 1534 g, 1.1 mmol) in OMF (10 mL) under stirring vyas treated with diethylphosphoryl cyanide 3 (0.179 g, 1.1 mmol) In OMF at 0°C, followed by the addition of triethylamine (0.212 g, 2 1 mmoO. The mixture was stirred for 30 min at 0°C and 4 h at 20 C The reaction mixture was diluted with PhH-EtOAc, washed with 5% HCI, water, 5% NaHCOs solution and bnne. Evaporation of the solvent gave crude 4 which after sIDca gel chromatography afforded 0.271 g of 4 (66%) (pure L), mp 1S8-160°C. 

Glycine ethyl ester hydrochloride [623-33-6] M 136.9, m 145-146", pK 7.69. Crystd from absolute EtOH. 

Aminobenzophenone Glycine ethyl ester hydrochloride Nitric acid... 

A mixture of 16.8 g of 2-aminobenzophenone, 11.9 g of glycine ethyl ester hydrochloride and 200 cc of pyridine was heated to reflux. After one hour, 20 cc of pyridine was distilled off. The solution was refluxed for 15 hours, then 11.9 g of glycine ethyl ester hydrochloride was added and the refluxing was continued for an additional 4 hours. The reaction mixture was continued for an additional 4 hours. The reaction mixture was concentrated in vacuo, then diluted with ether and water. The reaction product, 5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one, crystallized out, was filtered off, and then recrystallized from acetone in the form of colorless rhombic prisms, MP 182°Cto 183°C. 

Glycine ethyl ester hydrochloride, 14, 46 16, 86 17, 92 Grignard reaction in -butyl ether, 11, 84 with acetaldehyde, 12, 48 with butyl p-toluenesulfonate, 10, 4 with carbon dioxide, 11, 80 with dimethyl sulfate, 11, 66 with ethyl carbonate, 11, 98... 

Glycine ethyl ester hydrochloride, methyl formate, and triethylamine were purchased from Aldrich Chemical Company, Inc., and were used without purification. 

A solution of 140 g. (1 mole) of glycine ethyl ester hydrochloride 1 and 3 g. of sodium acetate in 150 ml. of water is added to the flask and cooled to 2° by means of an ice-salt bath. A cold solution of 80 g. (1.15 moles) of sodium nitrite in 100 ml. of water is added, and the mixture is stirred until the temperature has fallen to 0°. The temperature is maintained below 2°, and stirring is continued throughout all the following operations. To the cold mixture are added 80 ml. of cold, alcohol-free ethyl ether (Note 1) and 3 ml. of cold 10% sulfuric acid. After 5 minutes, the reaction mixture is blown over into the 1-1. separatory funnel by application of air pressure. The lower aqueous layer is quickly sucked back into the reaction flask. The ether layer is removed and immediately washed with 50 ml. of cold 10% sodium carbonate solution. This ether solution should be neutral to moist lilmus paper if not, the washing with sodium carbonate is repeated. The ether solution is finally dried over 10 g. of anhydrous sodium sulfate. 

Ethyl diazoacetate has been prepared by the action of sodium nitrite on glycine ethyl ester hydrochloride.3... 

We calculated the weight percentages of sodium ions in this series of sample solutions in the same way as described in the previous paper (8). By mixing O-aminoacyl sugar with sodium chloride, the weight percentage of sodium ions was reduced to around 10 % of that conventionally used, while the saltiness was maintained at the same level. Sodium ion diet effects of omithyl-p-alanine, glycine ethyl ester hydrochloride and basic amino acids were 75 %, 50 % and 25 %, respectively (8). O-... 

Glycine ethyl ester hydrochloride. Esterify 15 g (0.2 mol) of glycine in 100 ml of absolute ethanol with the aid of about 10 g of dry hydrogen chloride in the manner described for the preparation of glycylglycine ethyl ester hydrochloride (Expt 8.38). Recrystallise the product from the minimum of absolute ethanol. The yield of glycine ethyl ester hydrochloride, m.p. 144 °C, is 18.5 g (66%). 

Glycine ethyl ester hydrochloride (Sigma) make up as a 1-M stock and adjust to pH 8.0 with NaOH. 

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