Cyanide reaction with formaldehyde

The derivative from an isomeric fused system has been described as a sedative-hypnotic compound. The synthesis starts by condensation of the aminopicoline 32 with the haloketone 33. The resulting pyrrolo[l,2-a]pyridine 34 then undergoes a Mannich reaction with formaldehyde and dimethylamine to give the aminomethylated derivative 35. After quatemization of the di-methylamino group in 35 with methyl iodide, the ammonium group is displaced by cyanide to... 

The synthesis of zolpidem began with an alkylation/condensation reaction of amino-pyridine 5 and bromide 6 to give imidazopyridine 7 (Scheme 15.1). Mannich-type reaction with formaldehyde and dimethylamine provided 8. Treatment of 8 with methyliodide to form the quaternary salt 9, followed by reaction with sodium cyanide, gave 10. Acidic hydrolysis followed by reaction of the resultant acid 11 with carbonyldiimidazole (GDI) and dimethylamine afforded zolpidem (1) in 46% overall yield (George et al., 1991 Rossey and Long, 1988). 

As a further illustration of the reactivity of the 3 position toward electrophiles, the methoxyindole (25-1) readily undergoes Mannich reaction with formaldehyde and dimethylamine to afford the aminomethylated derivative (25-2). Treatment of that intermediate with potassium cyanide leads to the displacement of dimethylamine and the formation of the nitrile (25-3), possibly by an elimination-addition sequence involving a 3-exomethylene-indolenine intermediate. The protons on the methylene group adjacent to the nitrile are quite acidic and readily removed. Reaction of (25-3) with methyl carbonate in the presence of sodium methoxide gives the carbo-methoxylated derivative (25-4). Catalytic hydrogenation leads to reduction of the nitrile to a primary amine. There is thus obtained the antihypertensive agent indorenate (25-5) [26]. 

Indole (I) condenses with formaldehyde and dimethylamine in the presence of acetie acid (Mannich reaction see Section VI,20) largely in the 3-position to give 3 dimethylaminomethylindole or gramine (II). The latter reaets in hot aqueous ethanol with sodium cyanide to give the nitrile (III) upon boiling the reaction mixture, the nitrile undergoes hydrolysis to yield 3-indoleaeet-amide (IV), part of which is further hydrolysed to 3-indoleacetic acid (V, as sodium salt). The product is a readily separable mixture of 20 per cent, of (IV) and 80 per cent, of (V). 

Other methods of production iaclude hydrolysis of glycolonittile [107-16 ] with an acid (eg, H PO or H2SO2) having a piC of about 1.5—2.5 at temperatures between 100—150°C glycolonittile produced by reaction of formaldehyde with hydrogen cyanide recovery from sugar juices and hydrolysis of monohalogenated acetic acid. None of these has been commercially and economically attractive. 

EDA reacts with formaldehyde and sodium cyanide under the appropriate alkaline conditions to yield the tetrasodium salt of ethylenediaminetetraacetic acid (24). By-product ammonia is removed at elevated temperatures under a partial vacuum. The free acid or its mono-, di-, or trisodium salts can be produced by the appropriate neutrali2ation using a strong mineral acid. This same reaction with other amines is used to produce polyamino acetic acids and their salts. These products are used widely as chelating agents. 

Cyanide and thiocyanate anions in aqueous solution can be determined as cyanogen bromide after reaction with bromine [686]. The thiocyanate anion can be quantitatively determined in the presence of cyanide by adding an excess of formaldehyde solution to the sample, which converts the cyanide ion to the unreactive cyanohydrin. The detection limits for the cyanide and thiocyanate anions were less than 0.01 ppm with an electron-capture detector. Iodine in acid solution reacts with acetone to form monoiodoacetone, which can be detected at high sensitivity with an electron-capture detector [687]. The reaction is specific for iodine, iodide being determined after oxidation with iodate. The nitrate anion can be determined in aqueous solution after conversion to nitrobenzene by reaction with benzene in the presence of sulfuric acid [688,689]. The detection limit for the nitrate anion was less than 0.1 ppm. The nitrite anion can be determined after oxidation to nitrate with potassium permanganate. Nitrite can be determined directly by alkylation with an alkaline solution of pentafluorobenzyl bromide [690]. The yield of derivative was about 80t.with a detection limit of 0.46 ng in 0.1 ml of aqueous sample. Pentafluorobenzyl p-toluenesulfonate has been used to derivatize carboxylate and phenolate anions and to simultaneously derivatize bromide, iodide, cyanide, thiocyanate, nitrite, nitrate and sulfide in a two-phase system using tetrapentylammonium cWoride as a phase transfer catalyst [691]. Detection limits wer Hi the ppm range. 

REPPE PROCESS. Any of several processes involving reaction of acetylene (1) with formaldehyde to produce 2-butync-l,4-diol which can be converted to butadiene (2) with formaldehyde under different conditions to produce propargyl alcohol and, form this, allyl alcohol (3) with hydrogen cyanide to yield acrylonitrile (4) with alcohols to give vinyl ethers (5) with amines or phenols to give vinyl derivatives (6) with carbon monoxide and alcohols to give esters of acrylic acid (7) by polymerization to produce cyclooctatetraene and (8) with phenols to make resins. The use of catalysis, pressures up to 30 atm, and special techniques to avoid or contain explosions are important factors in these processes. 

N 27.45% liq, bp 69-70° at 13mm with si decomp explodes on heating rapidly mod sol in w can be prepd by dry distillation of the addn product from iodoacetonitrile (ICH2.CN) silver nitrate (AgNOg) or by reaction of formaldehyde Na cyanide, followed by nitration. This expl is not detonated by impact. It is stable in dry air, but in the presence of moisture develops acidity. It also develops pressure decomposes when stored in a closed vessel... 

With acid catalysis, alcohols add to the carbonyl group of aldehydes to give hemiacetals [RCH(OH)OR ]. Further reaction with excess alcohol gives acetals [RCH(OR )2]- Ketones react similarly. These reactions are reversible that is, acetals can be readily hydrolyzed by aqueous acid to their alcohol and carbonyl components. Water adds similarly to the carbonyl group of certain aldehydes (for example, formaldehyde and chloral) to give hydrates. Hydrogen cyanide adds to carbonyl compounds as a carbon nucleophile to give cyanohydrins [R2C(OH)CN],... 

The final polycyclic aromatic hydrocarbon that was investigated <2000EJ0335> is benzo[fixed double bond like phenanthrene. Its cross-ozonolysis with formaldehyde gave none of the normal ozonide 120, but mainly the aldehydic ozonide 117. At room temperature, a substantial amount of opening of the ozonide ring occurred with the formation of the acid aldehyde 121. Both products 117 and 121 could be stabilized by treatment with O-methylhydroxylamine, yielding products 118 and 122, respectively. The separate co-ozonolysis of compound 117 with vinyl acetate afforded the diozonide 119 (Scheme 37 and Table 16). The cross-ozonolysis with acetyl cyanide followed by treatment of the crude reaction mixture with O-methylhydroxylamine yielded the O-methyloxime of the cross-product. Cross-ozonolysis with benzoyl cyanide was not successful, and only the normal mono-ozonide 120 was formed. 

The second method makes use of the modified Streckter synthesis [9], First, hydrogen cyanide is reacted with formaldehyde to produce cyanohydrine. The latter compound is condensed with ethylenediamine to produce ethylenediamine tetracyanomethylene. Hydrolysis of the this compound produces the free acid. These reactions are schematically represented by Scheme 2. 

Nickel carbonyl is the catalyst for these reactions. In another Reppe process, acetylene is reacted with formaldehyde to yield butyndiol, which can be converted to butadiene for the manufacture of the synthetic rubber Buna the catalyst is nickel cyanide ... 

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