Cyanations

Another important class of reactions involves the introduction of a cyano group by substitution in an Ar-Z precursor. In fact, novel pathways leading to aromatic nitriles-for example, photosubstitution reactions-are desirable in view of the many applications of aryl cyanides as agrochemicals and pharmaceuticals. Today, the classical copper(l)-mediated Rosenmund-von Braun and Sandmeyer reactions, from aryl halides and aryldiazonium salts respectively, have been supplanted by reactions which employ palladium- or copper-catalysis [57]. The rather common use of excess cyanide anion may lead to a deactivation of the catalyst, and affect to a remarkable extent each of the key steps of the catalytic cycle [58aj. Although the use of complex iron cyanide has been shown to offer an effective solution to this limitation [58b,c], photocyanation provides an equally useful alternative [10], 

An attack at an unsubshtuted posihon was obtained via the addition of cyanide to the radical cation of an arene, and subsequent rearomatization. A recent example of this strategy is provided by the photocyanation of pyrene in the presence of DCB and NaCN in an oU-in-water emulsion system to give 1-cyanopyrene in 83% yield [63]. The direct formation of a o-complex from the triplet was envisaged in the photocyanation of 2-halo-4-nitroanisoles in a acetonitrile water solution (1 2), where the relative rates for the attack by cyanide on the halogenated compounds were in the ratio 27 2 2 1 for F, Cl, Br and 1, respectively [64]. 

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Urea (the diamide of carbonic acid) can be prepared by the historic method of Wohler. When an aqueous solution of ammonium cyanate is allowed to stand, the cyanate undergoes molecular rearrangement to urea, and an equilibrium mixture containing about 93% of urea is thus formed. Urea is... 

Ammonium cyanate, because of its instability in solution, is usually prepared (NHJaSO, + 2KCNO 2NH4CNO + KjSO by mixing aqueous solutions of ammonium sulphate and potassium cyanate. Complete evaporation then gives a mixture of potassium sulphate and urea, from which the urea may be extracted w ith hot absolute ethanol, in which potassium sulphate is insoluble. 

When the potassium cyanate used in the above preparation is replaced by potassium thiocyanate (or sulphocyanide), the ammonium thiocyanate formed undergoes partial rearrangement to thiourea (or sulpho-urea). Even above... 

Mono-substituted and unsymmetrical di-substituted ureas may be prepared by a modification of Wohler s urea synthesis, salts of primary or secondary amines being used instead of the ammonium salt for interaction with potassium cyanate. Thus when an aqueous solution containing both aniline hydrochloride and potassium cyanate is heated, aniline cyanate is first formed, and then C,HjNH,HCl -h KCNO = C,H6NHj,HCNO -h KCl C,HsNH HCNO = C.H NHCONH, by the usual molecular rearrangement is converted into monophenyburea. 

Dissolve 5 g. of aniline hydrochloride in 120 ml. of hot water contained in a 200 ml. conical flask and then add 4 g. of potassium cyanate. Heat the solution on a water-bath for 30 minutes, adding about 1-2 g. of animal charcoal towards the end of the heating if a slight turbidity has developed. Now bring the solution quickly to the boil over a gauze, and filter it at the pump, using a Buchner funnel and flask which have been preheated by the filtration of some boiling distilled water. The clear... 

These substances, having the formula CjHjNHCONH, and OC(NHCjH6)j respectively, are both formed when an aqueous solution of urea and aniline hydrochloride is heated. Their subsequent separation is based on the fact that diphenylurca is insoluble in boiling water, whereas monophenylurea is readily soluble. The formation of these compounds can be explained as follows. When urea is dissolved in water, a small proportion of it undergoes molecular rearrangement back to ammonium cyanate, an equilibrium thus being formed. 

The ammonium cyanate then reacts with the aniline hydrochloride giving aniline cyanate which, as in the previous preparation, gives in turn monophenylurea. 

A portion of the monophenylurea then reacts with the aniline (formed by the hydrolysis of the aniline hydrochloride or cyanate) to give diphenyl-urea and ammonia, a reaction which probably proceeds through the... 

Wohler s classical synthesis of urea from ammonium cyanate may be carried out by evaporating solutions of sodium cyanate and ammonium sulphate ... 

In aqueous solution at 100° the change is reversible and equilibrium is reached when 95 per cent, of the ammonium cyanate has changed into urea. Urea is less soluble in water than is ammonium sulphate, hence if the solution is evaporated, urea commences to separate, the equilibrium is disturbed, more ammonium cyanate is converted into urea to maintain the equilibrium and evfflitually the change into urea becomes almost complete. The urea is isolated from the residue by extraction with boiling methyl or ethyl alcohol. The mechanism of the reaction which is generally accepted involves the dissociation of the ammonium cyanate into ammonia and cyanic acid, and the addition of ammonia to the latter ... 

Thiourea (II) may be obtained from ammonium thiocyanate (I) by an isomeric change analogous to ammonium cyanate, but the equilibrium relationship is very different (compare Section 111,133) ... 

Salts of primary aromatic amines react with solutions of alkali cyanates to yield first the amine cyanate, which then undergoes molecular rearrangement to the arylurea, for example ... 

The monoarylurea may be prepared directly from the amine by heating it in aqueous solution with an equivalent quantity of alkali cyanate and excess of acetic acid, for example ... 

Method 1 (from the amine hydrochloride). Dissolve 13 Og. of anihne hydrochloride in 200 ml. of water and filter, if necessary, from any insoluble matter into a 350 ml. beaker or conical flask. Add a solution of 6-5 g, of pure sodium cyanate in 50 ml. of warm water. Allow to stand for a few hours until crystallisation is complete. Filter with suction on a Buchner funnel, and wash with a little cold water. Dry in the steam... 

The mechanism of the reaction involves the intermediate formation of an amine cyanate (see previous Section) in aqueous solution urea behaves as an equifi-brium mixture with ammonium cyanate ... 

The following alternative method may be used. Dissolve 0 01 mol of the phenol and 0 01 mol of a-naphthyl wo-cyanate in 20 ml. of light petroleum (b.p. 60-80°), add 2 drops of triethylamine (or, less satisfactorily, 2 drops of pyridine), reflux for 5 minutes, and allow to crystallise. Filter oflF the crystalline sohd through a sintered glass funnel. 

Hydrazine sulphate reacts with sodium cyanate in the presence of sodium carbonate to give semicarbazide, which remains in solution ... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Some organosilicon compounds undergo transmetallation. The allylic cyanide 461 was prepared by the reaction of an allylic carbonate with trimethylsi-lyl cyanide[298]. The oriho esters and acetals of the o. d-unsaturated carbonyl compounds 462 undergo cyanation with trimefhylsilyl cyanide[95]. 

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