Potassium Acetate Solution Cyanide

Methoxy-D-Homo-estra-l,3,5(10)-trien-17a-one (96)" (/) Acetic acid (6.4 ml) is added to a stirred solution of estrone methyl ether (93 1.1 g) in ethanol (35 ml) containing potassium cyanide (6 g) at 0°. After being stirred for 1 hr at 0° and 2.5 hr at room temperature, the reactants dissolve and potassium acetate preciptates. Water (65 ml) is added to the reaction mixture and the precipitated solid is collected by filtration. The crude product is dissolved in ethyl acetate and the ethyl acetate solution is washed with water, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. Recrystallization of a portion of the crude product from cyclohexane-acetone gives 3-methoxy-17a-cyano-estra-l, 3,5(10)-trien-17j5-ol (94a) as needles mp 158.5°. 

Benzyl cyanide is first reacted with 2-butylbromide in the presence of sodium amide to give 2-phenyl-3-methylvaleronitrile which is hydrolyzed by sulfuric acid to give 3-methyl-2-phenyl-pentanoic acid. 24 g of 2-phenyl-3-methyl-pentanoic acid are heated for one hour at 175° to 185°C with 30 g of 2-diethylaminoethanol and 0.5 g of sodium methylate. The excess diethyl-aminoethanol is removed in vacuo, the residue is dissolved in 300 cc of 2 N-acetic acid, the acid solution is shaken with ether and made alkaline with concentrated potassium carbonate solution and ice. The ether solution Is washed with water, dried with sodium sulfate and evaporated. The residue is distilled under high vacuum, yielding 20 to 21 g of the basic ester (60% of the theoretical) is obtained, the ester boiling at 98° to 100°C at a pressure of 0.03 mm. The hydrochloride of the ester melts at 112° to 113°C and the methobromide at 100° to 101°C. 

To suppress the noncatalyzed reaction (which decreases the enantioselec-tivity) between acetone cyanohydrin and the substrate, ethyl acetate is required as a co-solvent, and a low reaction temperature is also essential. Han et al.22 found that in organic solution with a trace amount of water the above reaction proceeds with the same high enantioselectivity as in the presence of an aqueous buffer. The reaction can be carried out at a wide range of temperatures from 0° to 30° C. To avoid using highly toxic potassium or sodium cyanide, acetone cyanohydrin is used as a cyano donor. 

There are several salts that behave in this way at atmospheric temperatures, the more important being ammonium acetate potassium bromate, carbonate, cyanide, ferricyanide, ferrocyanide, iodate, and permanganate disodium hydrogen phosphate and sodium borate and carbonate.4 In the case of potassium chlorate the points L and S appear to be practically coincident, whilst for the majority of salts the point S lies somewhere to the left of L, namely at S —that is to say, saturation occurs before the limiting concentration is reached. Generally speaking, at the ordinary temperature, concentrated solutions of salts are less corrosive than distilled water—that is, the point S lies below the level of A, exceptions being 5 ammonium sulphate, aluminium... 

With an aqueous suspension or a potassium iodide solution of iodine, only niereuTie iodide is isolated, Perniaiiganate in the presence of sulphuric acid converts it directly to carbon dioxide and mercuric salts, whereas Hofmann stated that triehloromercuri acetic acid was formed. Later, Hofmann admitted that his compound was so rapidly hydrolysed by water that he could not obtain a preparation free from oxygen. He therefore considered his compound to be an aldehyde. When heated with aqueous potassium cyanide, triehloromercuri acetaldehyde yields aldehyde resin, mercuric cyanide, and metallic mercury. No precipitate is formal when acetylene is passed througii an aqueous solution of mercuric chloride containing an excess of sodium chloride,... 

Calcium cyanide can be analyzed by titration with silver nitrate using potassium iodide indicator. Sulfide interfering in the reaction is removed by sodium carbonate-lead acetate solution. 

A concentrated solution of monochloroacetic acid is neutralised with sodium bicarbonate, and then heated with potassium cyanide, whereby sodium cyano-acetate is obtained ... 

Complexing agents, which act as buffers to help control the pH and maintain control over the free metal—salt ions available to the solution and hence the ion concentration, include citric acid, sodium citrate, and sodium acetate potassium tartrate ammonium chloride. Stabilizers, which act as catalytic inhibitors that retard the spontaneous decomposition of the bath, include fluoride compounds thiourea, sodium cyanide, and urea. Stabilizers are typically not present in amounts exceeding 10 ppm. The pH of the bath is adjusted. 

Hydroxy-B-homo-5a-cholestan-7-one acetate (54b) A solution of 3/3-hydroxy-5a-cholestan-7-one acetate (51b 5 g mp 146-148°) in dioxane-ethanol (100 ml, 1 1) is placed in a 250 ml three-necked flask equipped with a mechanical stirrer and thermometer and is cooled to 0° (iee-salt bath). Powdered potassium cyanide (7.3 g) is added portionwise with stirring. Acetic acid (8 ml) is then added dropwise with constant stirring over 30 min. The resultant mixture is stirred for 1 hr at 0° C and for an additional 2 hr at room temperature. It is then poured into ice water (200 g ice, 100 ml water) and after standing for 1 hr the precipitate is collected by filtration. The product is dissolved in ether (100 ml), the ether solution is washed with 5% sodium bicarbonate, water and dried over anhydrous sodium sulfate. The filtrate is evaporated at reduced pressure and the solid residue (5.1 g) is crystallized from ethyl acetate (30 ml) to yield 2.8 g of cyanohydrin (52b) mp 160-164° repeated crystallization from the same solvent gives a product mp 164-167°. An alternative method of isolation of the cyanohydrin is used when 100 g or larger quantities are worked up. The reaction mixture is poured directly into a mixture of ice water and sodium bicarbonate, the precipitate (mp 155-156°) is washed well with water, dried and used directly for the next step. 

The following technique is described in U.S. Patent 2,541,104. A solution of 2.0 g of 3(a )-hydroxy-21-acetoxy-11,20-diketo-pregnane, which can be prepared as described in Helv. Chim. Acta 27, 1287 (1944), is treated in a mixture of 25 cc of alcohol and 6.4 cc of acetic acid at 0°C with 6.0 g of potassium cyanide. The solution is allowed to warm to room temperature and after 3 hours is diluted with water. The addition of a large volume of water to the alcohol-hydrogen cyanide mixture precipitates a gum which is extracted with chloroform or ethyl acetate. The extract is washed with water, and evaporated to small volume under reduced pressure. The crystalline precipitate (1.3 g) consists of 3(a ),20-dihvdroxy-20-cvano-21-acetoxy-11-keto-pregnane dec. 175° to 185°C. 

The reaction is a sensitive one, but is subject to a number of interferences. The solution must be free from large amounts of lead, thallium (I), copper, tin, arsenic, antimony, gold, silver, platinum, and palladium, and from elements in sufficient quantity to colour the solution, e.g. nickel. Metals giving insoluble iodides must be absent, or present in amounts not yielding a precipitate. Substances which liberate iodine from potassium iodide interfere, for example iron(III) the latter should be reduced with sulphurous acid and the excess of gas boiled off, or by a 30 per cent solution of hypophosphorous acid. Chloride ion reduces the intensity of the bismuth colour. Separation of bismuth from copper can be effected by extraction of the bismuth as dithizonate by treatment in ammoniacal potassium cyanide solution with a 0.1 per cent solution of dithizone in chloroform if lead is present, shaking of the chloroform solution of lead and bismuth dithizonates with a buffer solution of pH 3.4 results in the lead alone passing into the aqueous phase. The bismuth complex is soluble in a pentan-l-ol-ethyl acetate mixture, and this fact can be utilised for the determination in the presence of coloured ions, such as nickel, cobalt, chromium, and uranium. 

Potassium cyanide (71.6 g., 1.1 moles, u.s.p.) and 100 ml. of 95% ethanol are placed in a 2-1. round-bottomed flask having a ground joint and arranged with a Hershberg stirrers (Note 1). A solution of 113 g. (106 ml., 1 mole) of ethyl cyanoacetate, 79 g. (98 ml., 1.1 moles) of 2-butanone, and 66 ml. of.glacial acetic acid is added to the stirred solution over a period of 1 hour. The mixture is stirred for an additional hour, the stirrer is removed, and the mixture is allowed to stand at room temperature for 7 days (Note 2). 

As esters the alkyl halides are hydrolysed by alkalis to alcohols and salts of halogen acids. They are converted by nascent hydrogen into hydrocarbons, by ammonia into amines, by alkoxides into ethers, by alkali hydrogen sulphides into mercaptans, by potassium cyanide into nitriles, and by sodium acetate into acetic esters. (Formulate these reactions.) The alkyl halides are practically insoluble in water but are, on the other hand, miscible with organic solvents. As a consequence of the great affinity of iodine for silver, the alkyl iodides are almost instantaneously decomposed by aqueous-alcoholic silver nitrate solution, and so yield silver iodide and alcohol. The important method of Ziesel for the quantitative determination of alkyl groups combined in the form of ethers, depends on this property (cf. p. 80). 

The ammine complexes of Co3+ are prepared by adding excess ammonia to a solution of cobalt salt followed by air oxidation and boding. The brown solution turns pink on boiling. The cyanide complexes are made by adding excess potassium cyanide to a solution of cobalt salt. Acidification of the solution with a small amount of acetic or hydrochloric acid followed by boiling yields K3Co(CN)6. The aquo-halo mixed complexes are formed by stepwise substitution of H2O molecule with halide ion in the coordination sphere. In general, a mixed complex may be prepared by substitution with a specific anion. 

Formylfuran behaves in a very similar manner to benzaldehyde and undergoes the usual reactions of an aromatic aldehyde, e.g. (i) the Cannizzaro reaction with cone, sodium hydroxide to give furan-2-ylmethanol and the sodium salt of furoic acid, (ii) the Perkin reaction with acetic anhydride and sodium acetate to yield an aldol product that dehydrates to 3-(furan-2-yl)propenoic acid, and (iii) a condensation with potassium cyanide in alcoholic solution to form furoin (under these conditions, benzaldehyde undergoes the benzoin condensation) (Scheme 6.32). 

Two hundred and five grams T1 mole) of a-phenylcinnamoni-trile,2 2250 ml. of methanol, and 750 ml. of ether are placed in a 5-1. round-bottomed flask fitted with a two-necked adapter supporting a 1-1. separatory funnel and reflux condenser. The a-phenylcinnamonitrile is dissolved by gentle heating, and the solution is heated under reflux. A solution of 274 g. (4 moles) of 95% potassium cyanide in 600 ml. of water (which has been preheated to 45°) is added rapidly from the separatory funnel (Note 1). A small amount of potassium cyanide precipitates. The solution is heated under reflux for 1 hour, after which a solution of 154 g. (2 moles) of ammonium acetate in 250 ml. of water is added rapidly from the separatory funnel (Note 2). 

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