Hydrogen cyanide protonated

The electrophile 4 adds to the aromatic ring to give a cationic intermediate 5. Loss of a proton from 5 and concomitant rearomatization completes the substitution step. Subsequent hydrolysis of the iminium species 2 yields the formylated aromatic product 3. Instead of the highly toxic hydrogen cyanide, zinc cyanide can be used. The hydrogen cyanide is then generated in situ upon reaction with the hydrogen chloride. The zinc chloride, which is thereby formed, then acts as Lewis acid catalyst. 

Another example of an acid is hydrogen cyanide, HCN, which transfers its proton to water when it dissolves to form the solution known as hydrocyanic acid, HCN(aq). However, only a small fraction of the HCN molecules donate their protons, and so we classify HCN as a weak acid in water. We write the proton transfer reaction with equilibrium half-arrows ... 

Most protic solvents have both protogenic and protophilic character, i.e. they can split off as well as bind protons. They are called, therefore, amphiprotic. These include water, alcohols, acids (especially carboxylic), ammonia, dimethylsulphoxide and acetonitrile. Solvents that are protogenic and have weak or practically negligible protophilic character include acid solvents, such as sulphuric acid, hydrogen fluoride, hydrogen cyanide, and formic acid. 

The asymmetric synthesis achieved when the base is an optically active one is proof that the base is present in a transition state with the carbonyl and not just an agent for removal of protons from hydrogen cyanide. It has further been shown that asymmetric synthesis is still achieved even if the only optically active molecules present are quaternary ammonium compounds, i.e., positive ions without any protons to donate. This probably means that the important thing is to have some positive ion near the carbonyl oxygen, an actual covalent... 

This MCR chemistry began in 1850 when the Strecker reaction S-3CR of ammonia, aldehydes, and hydrogen cyanide was introduced. Since 1912 the Mannich reaction M-3CR of secondary amines, formaldehyde, and (3-protonated ketones is used. 

Caution. The reagents trimethyltriazacyclonane and trifluoromethane sulfonic acid are harmful by inhalation and by contact with skin. Potassium cyanide is highly toxic and produces volatile, poisonous hydrogen cyanide on protonation. All operations must be conducted in a well-ventilated fume hood. Wear appropriate protective clothing, gloves, and eye protection. 

In the first chapter, D. S. Donald and O. W. Webster summarize much fundamental heterocyclic chemistry dealing with the preparation of heterocycles from hydrogen cyanide and its derivatives, mostly previously available only in the patent literature. In the second, the account of the ringopening of five-membered heteroaromatic anions by T. L. Gilchrist brings together the numerous transformations that can succeed the removal of a proton from a carbon atom in a five-membered heterocyclic ring. 

The preparation of amides by the addition of hydrogen cyanide or alkyl nitriles to alkenes in the presence of acids, known as the Ritter reaction, has been reviewed.229-232 The reaction may be considered simplistically as nucleophilic attack of a nitrile on a carbocation formed by the protonation of an alkene. Subsequent hydrolysis of the nitrilium intermediate gives the amide product (equation 164). The overall result is addition of a molecule of H—NHCOR to a C—C double bond. 

Cyanohydrin derivatives have also been widely used as acyl anion synthons. They are prepared from carbonyl compounds by addition of hydrogen cyanide. A very useful variant is to use trimethylsilyl cyanide with an aldehyde to produce a trimethylsilyloxy cyanide. The cyano group acidifies the a position (pKA 25) and the a proton can be removed by a strong base. Alkylation of the anion and unmasking of the hydroxy group cause elimination of cyanide and re-formation of the carbonyl group. 

Dissolve 20 g (0.13 mol) of the cyano ester in 100 ml of rectified spirit and add a solution of 19.2g (0.295 mol) of pure potassium cyanide (CAUTION) in 40 ml of water. Allow to stand for 48 hours, then distil off the alcohol on a water bath. Add a large excess of concentrated hydrochloric acid and heat under reflux for 3 hours. (CAUTION hydrogen cyanide evolved.) Dilute with water, saturate the solution with ammonium sulphate and extract with four 75 ml portions of ether. Dry the combined ethereal extracts with anhydrous sodium sulphate, and distil off the ether. Recrystallise the residual acid from excess concentrated hydrochloric acid, and dry in the air. The yield of pure 2,2-dimethylsuccinic acid, m.p. 141-142 °C, is 12 g (63%). The p.m.r. spectrum is recorded in trifluoracetic acid and reveals signals at S 1.48 (s, 6H, Me2) and 2.92 (s, 2H, CH2) the hydroxyl proton is not observed. 

These experiments show clearly that undissociated, gaseous HCN or HCN dissolved as gas shows no reactivity. An addition of small amounts of KCN to an aqueous sulfuric acid solution of Fe2+/Fe3+, however, results in the immediate precipitation of the pigment. The cyanide obviously reacts faster with the iron salts than it is protonated by sulfuric acid, i.e., converted into hydrogen cyanide. 

Fig. 2.23 shows the separation achieved on a 12 anion standard by this procedure. Sulphide, cyanide, bromide, and sulphite are detected at the silver electrode while nitrite, nitrate, phosphate and sulphate produce no response. Due to the low dissociation of hydrogen sulphide and hydrogen cyanide following protonation by the suppressor column, they are not detected by the conductivity detector. 

The reduction of a pyridinium ion in the presence of hydrogen cyanide has been shown to produce substituted 6-cyano-l,2,5,6-tetrahydropyridines. The cyanide competes with the borohydride ion for reaction with the protonated dihydropyxidine intermediate. The cyanide addition can be reversed, and this reaction, therefore, provides a method of protecting the intermediate dihydropyridine from reduction by sodium borohydride.47"... 

Studies of proton transfers from carbon with f1/2 less than one microsecond are quite rare. The ionization of hydrogen cyanide in aqueous alkaline solution has been studied [20] using the ultrasonic stationary method which is applicable to reactions with tl/2 in the range 10 5 to 10 9 sec. Several reactions of benzyl carbanion having f 1/2 in the range 10-6—5 x 10-8 sec have been studied in tetrahydrofuran. The carbanion was generated by pulse radiolysis of solutions of dibenzyl mercury and its subsequent reaction with water and alcohols was followed spectrophotometrically [21]. 

---