Sodium hydrogen carbonate reaction with acetic acid

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

The bulk material may ignite or explode in storage. Traces of water may initiate the reaction. A rapid exothermic decomposition above 175°C releases oxygen and chlorine. Moderately explosive in its solid form when heated. Explosive reaction with acetic acid + potassium cyanide, amines, ammonium chloride, carbon or charcoal + heat, carbon tetrachloride + heat, N,N-dichloromethyl-amine + heat, ethanol, methanol, iron oxide, rust, 1-propanethiol, isobutanethiol, turpentine. Potentially explosive reaction with sodium hydrogen sulfate + starch + sodium carbonate. Reaction with acetylene or nitrogenous bases forms explosive products. 

Here, a carbonate (sodium carbonate) reacts with an acid (hydrochloric acid) to produce a salt (sodium chloride), water, and carbon dioxide gas. A similar reaction is shown in Figure 4.10, in which baking soda (sodium hydrogen carbonate) reacts with the acetic acid in vinegar. Note the bubbles of carbon dioxide gas that evolve during the reaction. This reaction of a carbonate with an acid is the basis of a simple test for carbonate minerals. When you treat a carbonate mineral or rock, such as limestone, with hydrochloric acid, the material fizzes, as bubbles of odorless carbon dioxide form. 

To a solution of 10 g of 2-N-methyl-aminoacetamido-3-o-chlorobenzoyl-5-ethylthiophene in 50 ml of pyridine are added 20 ml of benzene and 1.9 g of acetic acid. The resulting mixture is refluxed with stirring for 10 hours in a flask provided with a water-removing adaptor. The reaction mixture is concentrated, and the residue is extracted with chloroform. The chloroform layer is washed with water and then with a sodium hydrogen carbonate solution, then dried over magnesium sulfate. The chloroform is distilled off under reduced pressure, and toluene is added to the residue. Thus is precipitated white crystalline-5-o-chloropheny -7-ethyl-1 -methyi-1,2-dihydro-3H-thieno-[2,3-e] [ 1,4] diazepin-2-one, MP 105°C to 106°C. 

A) A mixture of 333 parts of 4-(1 -piperazinyDphenol dihydrobromide, 11.2 parts of acetic acid anhydride, 42 parts of potassium carbonate and 300 parts of 1,4-dioxane is stirred and refluxed for 3 days. The reaction mixture is filtered and the filtrate is evaporated. The solid residue is stirred in water and sodium hydrogen carbonate is added. The whole is stirred for 30 minutes. The precipitated product is filtered off and dissolved in a diluted hydrochloric acid solution. The solution is extracted with trichloromethane. The acid aqueous phase is separated and neutralized with ammonium hydroxide. The product is filtered off and crystallized from ethanol, yielding 5.7 parts of 1 acetyl-4-(4-hydroxyphenyl)piperazine MP 181.3°C. 

Method B.104 In a 1-litre flask equipped with a condenser, a thermometer and a dropping funnel is placed 0.3 mol of lithium aluminium hydride (CAUTION, see Section 4.2.49, p. 445) in dry ether (300 ml). A nitrogen atmosphere is maintained throughout the reaction. To this stirred solution 0.45 mol of ethyl acetate is added over a period of 75 minutes maintaining the temperature at 3-7 °C. The reaction is stirred for an additional 30 minutes. To this solution at —10 °C is added 29.1 g (0.3 mol) of hexanenitrile in 5 minutes. The reaction temperature rises to 12°C in 10 minutes with the formation of a viscous solution. It is allowed to stir for another 50 minutes at 3 °C. The reaction mixture is decomposed by the addition of 300 ml of 2.5 m sulphuric acid. The ether layer is separated and the aqueous layer is extracted with ether. The combined ether extracts are washed with sodium hydrogen carbonate solution and water and dried over anhydrous sodium sulphate (1). 

Cognate preparations sulphuric acid catalyst. Ethyl butanoate. Use a mixture of 88 g (92 ml, 1 mol) of butanoic acid, 23 g (29 ml, 0.5 mol) of ethanol and 9g (5 ml) of concentrated sulphuric acid. Reflux for 14 hours. Pour into excess of water, wash several times with water, followed by saturated sodium hydrogen carbonate solution until all the acid is removed, and finally with water. Dry with anhydrous sodium sulphate, and distil. The ethyl butanoate passes over at 119.5-120.5 °C. Yield 40g (69%). An improved yield can be obtained by distilling the reaction mixture through an efficient fractionating column until the temperature rises to 125 °C, and purifying the crude ester as detailed above under methyl acetate. 

Benzyl acetate. Mix 31 g (29.5 ml, 0.287 mol) of benzyl alcohol (Expt 6.133) and 45 g (43 ml, 0.75 mol) of glacial acetic acid in a 500-ml round-bottomed flask introduce 1 ml of concentrated sulphuric acid and a few fragments of porous pot . Attach a reflux condenser to the flask and boil the mixture gently for 9 hours. Pour the reaction mixture into about 200 ml of water contained in a separatory funnel, add 10 ml of carbon tetrachloride (to eliminate emulsion formation owing to the slight difference in density of the ester and water, compare methyl benzoate, Expt 6.163) and shake. Separate the lower layer (solution of benzyl acetate in carbon tetrachloride) and discard the upper aqueous layer. Return the lower layer to the funnel, and wash it successively with water, concentrated sodium hydrogen carbonate solution (until effervescence ceases) and water. Dry over 5 g of magnesium sulphate, and distil from an air bath. Collect the benzyl acetate (a colourless liquid) at 213— 215°C. The yield is 16g (37%). 

In a 250-ml round-bottomed flask, provided with a small reflux condenser and a calcium chloride drying tube at the top, place 2.1 g (0.17 mol) of salicylaldehyde, 2.0 ml of anhydrous triethylamine and 5.0 ml (0.052 mol) of acetic anhydride, and reflux the mixture gently for 12 hours. Steam distil the mixture from the reaction flask and discard the distillate. Render the residue in the flask basic to litmus with solid sodium hydrogen carbonate, cool, filter the precipitated crude coumarin at the pump and wash it with a little cold water. Acidify the filtrate to Congo red with 1 1-hydrochloric acid, collect the precipitated o-acetoxycinnamic acid and recrystallise it from 70 per cent propan-2-ol the yield is 0.40 g (11%), m.p. 153-154 °C. 

Reflux 1 g of the sulphonamide with 2.5 ml of acetyl chloride for 30 minutes if solution is not complete within 5 minutes, add up to 2.5 ml of glacial acetic acid. Remove the excess of acetyl chloride by distillation on a water bath, and pour the cold reaction mixture into water. Collect the product, wash with water and dissolve it in warm sodium hydrogen carbonate solution. Acidify the filtered solution with glacial acetic acid filter off the precipitated sulphonacetamide and recrystallise it from aqueous ethanol. 

The residue was subjected to azeotropic operation with toluene two times, and ether was added to the residue. The precipitate derived from trioxane was removed by filtration and washed with ether, and the combined ethereal solutions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with water and aqueous saturated solution of sodium chloride, was dried, and was concentrated to give 4 g of an oily material. The oily material was dissolved in 20 ml of methanol and to the solution was added 20 ml of aqueous 1 N solution of sodium hydroxide, and the mixture was stirred for 14 hours at room temperature. After removal of methanol under reduced pressure, water was added to the mixture, and this solution was acidified to pH 3 with aqueous 2 N hydrochloric acid. The mixture was extracted five times with ethyl acetate, and the ethyl acetate extract was dried and concentrated to give 3.5 g of crude crystals. After addition of ethanol to the crude crystals, the crude crystals were filtered. The filtrate was concentrated, and to the residue was added ethanol and ethyl acetate, and precipitate was collected by filtration. The combined amount of the crude crystals was 1.6 g. After the combined crude crystals were methylated with diazomethane, the reaction product was dissolved in 20 ml of ethyl acetate. To this solution was added 1.5 g of sodium acetate and 300 mg of 10% palladium-carbon, and the mixture was stirred for 2 hours under hydrogen. Then, the reaction product was filtered, and after addition of aqueous saturated solution of sodium hydrogen carbonate to the filtrate, the mixture was extracted two times with ethyl acetate. The extract was washed with an aqueous saturated solution of sodium chloride, dried, and concentrated to give 1.3 g of crude crystals. The crude crystals were recrystallized from ethyl acetate to yield 765 mg of the title compound (melting point 134-135°C, yield 43%). 

To a solution of benzhydryl 2-p-azidomethyl-2-a-methylpenam-3-a-carboxylate (7.03 g) in a mixture of acetic acid (240 ml) and water (40 ml) was added potassium permanganate (6.02 g) over a period of more than 1 h. The mixture was stirred at room temperature for 2.5 h. The resulting reaction mixture was diluted with ice water. The precipitate was collected by filtration, and washed with water. The resulting product was dissolved in ethyl acetate and the solution was washed with an aqueous solution of sodium hydrogen carbonate and dried over magnesium sulfate. Concentration gave 5.48 g of the benzhydryl 2-p-azidomethyl-2-a-methylpenam-3-a-carboxylate-l, 1-dioxide in 72% yield. 

In 2 N hydrochloric acid (0.5 ml) was dissolved 2-(4-amino-3-carboxymethylphenyl)propionic acid disodium salt, 53 mg, 0.2 mmol). Sodium nitrite (14 mg, 0.2 mmol) was added to the resulting solution under stirring and chilling with ice. The mixture was stirred for 30 minutes under chilling with ice. The mixture was then neutralized with a chilled aqueous saturated sodium acetate solution. To the neutralized mixture was added a solution of thiophenol (0.02 ml, 0.2 mmol) in 6 N aqueous sodium hydroxide solution (0.1 ml), and the mixture was stirred for 2 hours at room temperature. The reaction mixture was then made acidic by addition of 2 N hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate portion was extracted with an aqueous saturated sodium hydrogen carbonate solution. The aqueous portion was then made acidic by addition of 6 N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate portion was washed successively with water and an aqueous saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 28 mg (yield 45%) of the 2-(3-carboxymethyl-4-phenylthiophenyl)propionic acid. 

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