Cyanate reactions

Decomposition of cyanic acid and cyanates to form ammonia and carbonate, with parallel reactions to form urea and substituted ureas has had much kinetic study. The major features of the overall reactions are well known . The reactions involved in urea formation have been summarized thoroughly from a mechanistic viewpoint e.g. Frost and Pearson Little treatment will be given here. 

Formation of carbonate and ammonia was underestimated for many years . It is presumed to involve intermediate formation of carbamic acid or carbamates. The reaction is not subject to general acid or base catalysis , but has long been known to be catalysed by carbonate. This catalytic reaction has been examined carefully . 

The rates of cyanate hydrolysis and of reaction of amines and cyanic acid may be explained in terms of steps (1) (7) 

Reactions (3) and (7) are included because the rate coefficients are known more accurately than are 2 and kg. There are also kinetically indistinguishable paths for other steps but there is no need to tabulate them. Typical rate data are given in Tables 6 and 7. 

Rate coefficient Temp. (°C) ft k (l.mole, sec ) Activation energy (kcal.mole Ref. 

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The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

The vapor-phase chlorination reaction occurs at approximately 200-300°C. The dichlorobutene mixture is then treated with NaCN or HCN in presence of copper cyanide. The product 1,4-dicyano-2-butene is obtained in high yield because allylic rearrangement to the more thermodynamically stable isomer occurs during the cyanation reaction ... 

There are many other examples in the literature where sealed-vessel microwave conditions have been employed to heat water as a reaction solvent well above its boiling point. Examples include transition metal catalyzed transformations such as Suzuki [43], Heck [44], Sonogashira [45], and Stille [46] cross-coupling reactions, in addition to cyanation reactions [47], phenylations [48], heterocycle formation [49], and even solid-phase organic syntheses [50] (see Chapters 6 and 7 for details). In many of these studies, reaction temperatures lower than those normally considered near-critical (Table 4.2) have been employed (100-150 °C). This is due in part to the fact that with single-mode microwave reactors (see Section 3.5) 200-220 °C is the current limit to which water can be safely heated under pressure since these instruments generally have a 20 bar pressure limit. For generating truly near-critical conditions around 280 °C, special microwave reactors able to withstand pressures of up to 80 bar have to be utilized (see Section 3.4.4). 

Scheme 6.S6 Transition metal-mediated cyanation reactions.

A series of potent, linear C2-symmetric HIV-1 protease inhibitors with K, values in the nanomolar range was prepared from a diaryl bromide precursor emanating from a carbohydrate scaffold, by application of Heck, Suzuki, Stille, and cyanation reactions. Included in this series was the first reported microwave-promoted Suzuki coupling with an alkyl borane [41]. A very high-yielding Suzuki coupling is presented... 

Another interesting cyanation reaction, also brought about by nickel(0)... 

When an anion exchange resin Amberlite IRA 400 [CN-] is used as a cyanating agent, the final products of the aldonitrone cyanating reaction are a-iminonitriles (Scheme 2.173) (Table 2.14) (634). 

Sodium cyanate, reaction with <-butyl alcohol and trifluoroacetic acid, 48,32... 

The cyanation reactions with (19) (extremely toxic and requires essentially nonacidic reaction conditions) can also he carried out with unprotected aldehydes in good yields but with higher charge consumption (88-97%, 0.15-0.45 F). For ketones, the products are isolated as trimethylsilyl ethers, whereas for aldehydes the sdyl ethers are hydrolyzed to alcohols [33]. 

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

Scheme 6.14 Product range of the 9-catalyzed acetyl cyanation reaction of aldimines with acetyl cyanide as the cyanide source.

Scheme 11.2 Some of the impurities identified in cyanation reaction.

Thus transition metal complexes capable of effecting cyanation reactions on aromatic nuclei under mild conditions have been discovered Cassar et al. describe such a catalytic system. The past few years have also seen the discovery of asymmetric catalysis. Asymmetric catalysts contain optically active ligands and, like enzymes, can promote catalytic reactions during which substantial levels of optical activity are introduced into the products. This volume contains examples of asymmetric hydrogenation and asymmetric hydroformylation catalysis in the papers, respectively, by Knowles et al. and Pino et al. 

The Cyanation Reaction. Three examples of the cyanation reaction and the general procedure for the determination of the relative rates are reported below. 

Catalyst of the Cyanation Reaction. The reaction was studied in the presence of Ni(0) complexes or aryl(chloro)nickel complexes. For a clearer interpretation the corresponding results are considered separately. A variant of the process consisting in the use of acetone cyanohydrin as source of cyanide ions is also reported. 

Tris(p-tolylphosphine) was used successfully in place of triphenyl-phosphine. The cyanation reaction appears to be a substitutive reaction, the cyano group always occurring on the carbon originally bound to the halogen. 

Influence of Solvent, Ligand, and Substrate Substituents. These factors appear to play a very important role in the cyanation reaction. 

In general these reactions do not interefere with cyanation. Reaction 7 is a catalytic process (14) and is strongly favored by electron-releasing substituents on the aromatic halide. In fact in the case of p-aminochloro-benzene, formation of the phosphonium salt competes with the cyanation process. 

Stoichiometric Cyanation Reaction. To elucidate the mechanism, the stoichiometric cyanation reaction of tram-chloro (aryl) bis (triphenylphos-phine) nickel (II) complexes 1 was studied. Arylnickel (II) complexes... 

A comparison of Figures 2 and 4 indicates that substituents have a qualitatively similar effect both on the oxidative addition reaction and on the catalytic cyanation. In both cases in fact there is a change in the slope on passing from electron-withdrawing to electron-releasing substituents. As to the effect of electron-withdrawing substituents, the sensitivity is lower in catalytic cyanation (p = 4.8) than in oxidative addition (p = 8.8) which is what is to be expected on the basis of the substituent effect in stoichiometric cyanation reaction of arylnickel complexes. 

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