Copper cyanates

The reaction is effectively catalysed by divalent copper ions, which are often released from the distillation apparatus. By another reaction copper cyanate is produced, and nucleophilic addition of water gives rise to copper carbamate, which provides ethyl carbamate by alcoholysis or decomposes to copper hydroxide, carbon dioxide and ammonia. 

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 ... 

Arylthallium bis(trifluoroacetate)s (10.70) are versatile synthons for various reactions, e.g., acylations (Larock and Fellows, 1982) and photolytic cyanations (Taylor et al., 1970), as shown in Scheme 10-93. Copper-catalyzed cyanations (Uemura et al., 1972) can be carried out at 115 °C with arylthallium (acetate)(perchlorate) (Scheme 10-94). 

Vinylic copper reagents react with CICN to give vinyl cyanides, though BrCN and ICN give the vinylic halide instead." Vinylic cyanides have also been prepared by the reaction between vinylic lithium compounds and phenyl cyanate PhOCN." Alkyl cyanides (RCN) have been prepared, in varying yields, by treatment of sodium trialkylcyanoborates with NaCN and lead tetraacetate." Vinyl bromides reacted with KCN, in the presence of a nickel complex and zinc metal to give the vinyl nitrile. Vinyl triflates react with LiCN, in the presence of a palladium catalyst, to give the vinyl nitrile." ... 

Aqueous cyanide effluent containing a little methanol in a 2 m3 open tank was being treated to destroy cyanide by oxidation to cyanate with hydrogen peroxide in the presence of copper sulfate as catalyst. The tank was located in a booth with doors. Addition of copper sulfate (1 g/1) was followed by the peroxide solution (27 1 of 35 wt%), and after the addition was complete an explosion blew off the doors of the booth. This was attributed to formation of a methanol vapour-oxygen mixture above the liquid surface, followed by spontaneous ignition. It seems remotely possible that unstable methyl hydroperoxide may have been involved in the ignition process. 

The same group of authors has recently reported a combination of various palladium- and copper-catalyzed Suzuki, cyanation, and Ullmann condensation reactions for the synthesis of thiophene-based selective angiotensin II AT2 receptor antagonists (Scheme 6.24) [55],... 

Our new approach has proven its initial value in both palladium-(Schareina et al. 2004) and copper-catalyzed cyanations (Schareina et al. 2005) and has been adopted by other groups. Very recently, in a joint collaboration with Saltigo GmbH we developed a new and improved copper-based catalyst system, which allows for efficient cyanations of a variety of aromatic and heteroaromatic halides. Importantly, notoriously difficult substrates react in excellent yield and selectivity, making the method applicable on an industrial scale. 

The similarities and differences between copper-catalyzed oxycyanation and diacetoxy-lation (vide supra), which are summarized in Figure 3, have been discussed. The main difference in the regiochemistry of the two reactions, i.e. an almost exclusive 1,4-addition in the cyanation and a non-regioselective acetoxylation, has been emphasized but was not interpreted in mechanistic terms. 

Although there have been few new developments in the period since 1993, halogenopyrazines 42 have been convenient precursors for a variety of pyrazine derivatives. For example, the halogenopyrazines 42 are cyanated by palladium-catalyzed cross-coupling with alkali cyanide or by treatment with copper cyanide in refluxing picoline, to yield cyanopyrazines 48. Alkoxypyrazines 49 are produced by treatment with alkoxide-alcohol, and aminopyrazines 50 are prepared by amination with ammonia or appropriate amines. The nucleophilic substitution of chloropyrazine with sodium alkoxide, phenoxide, alkyl- or arylthiolate is efficiently effected under focused microwave irradiation <2002T887>. 

Sodium cyanide solution dissolves certain metals (I) with absorption of oxygen, e.g.. gold, silver, mercury, lead, and (2) with evolution of hydrogen, e.g.. copper, nickel, iron. zinc, aluminum, magnesium and solid sodium cyanide, when heated with certain oxides, e.g.. lead monoxide PhO. stannic oxide SnO.. yields the metal of the oxide, e.g.. lead. tin. respectively. and sodium cyanate NaCNO. Two classes of esters arc known, cyanides or nitriles, and isocyanides, isonitriles or carbylatnincs. the latter being very poisonous and of marked nauseating odor... 

Fig. 1. Simultaneous separation and detection of anions and cations on a latex agglomerate column. Column Dionex HPIC-CS5 cation exchange column (250X2 mm) with precolumn HPIC-CG5 (50 X 4 mm) eluent 0.5 mM copper sulfate, pH 5. 62 flow rate 0.5 ml/min sample volume 20 gl containing 0.1 m M of each ion detection two potentiomet-ric detectors equipped with different ion-selective electrodes in series. Peaks (1) chloroacetate, (2) chloride, (3) nitrite, (4) benzoate, (5) cyanate, (6) bromide, (7) nitrate, (8) sodium, (9) ammonium, (10) potassium, (11) rubidium, (12) cesium, (13) thallium. Reprinted with permission from [10].

In 2003, Leadbeater and co-workers reported a related copper iodide mediated cyanation of aryl iodides in water with TBAB as an essential additive57. Stoichiometric quantities of Cul were needed in this protocol, as the use of catalytic quantities resulted in significantly lower yields. 

Figure 4-35. The copper(n) mediated reaction of cyanate with 3,5-dimethylpyrazole.

In the case of amine nucleophiles, the products from the reaction with co-ordinated cyanates are carbamates or ureas (Fig. 4-34), and this provides a particularly convenient method for the preparation of carbamate complexes. An example of this behaviour is seen in the reaction of 3,5-dimethylpyrazole with cyanate in the presence of copper(n) salts (Fig. 4-35). Similar reactions are observed with co-ordinated thiocyanates and other heterocumulene s. 

Aryl nitriles can be prepared by the cyanation of aryl halides with an excess of copper(I) cyanide in a polar high-boiling solvent such as DMF, nitrobenzene, or pyridine at reflux temperature. 

The excess of copper cyanide and the use of a polar, high-boiling point solvent makes the purification of the products difficult. In addition, elevated temperatures (up to 200°C) lower the functional group tolerance. The use of alkali metal cyanides or cyanation reagents such as cyanohydrins, a catalytic amount of copper(I) iodide and kalium iodide, allows a mild, catalytic cyanation of various aryl bromides. 

Sulfuric acid, concentrated and dilute Silver nitrate Copper sulfate-pyridine test Cyanates, OCN Vigorous effervescence, due largely to evolution of carbon dioxide, with concentrated acid producing a more dramatic effect Curdy white precipitate of silver cyanate Lilac-blue precipitate (interference by thiocyanates) reagent is prepared by adding 2 or 3 drops of pyridine to 0.25 M CuS04 solution... 

The oxazolidin-2-ones 53 (R = H=CCH=CH2 or COEt) are obtained in a one-pot reaction of amino alcohol carbamates 52 with sodium hydroxide, followed by allyl bromide or propi-onyl chloride (94TL9533). A modified procedure for the preparation of chiral oxazolidin-2-ones 56 from a-amino acids 54, which avoids the hazardous reduction of the acids with borane and the intermediacy of water-soluble amino alcohols, is treatment of the methyl ester of the amino acid with ethyl chloro-formate to give 55, followed by reduction with sodium borohydride and thermal ring-closure of the resulting carbamate f95SC561). The 2-prop-ynylcarbamates 57 (R = Ts, Ac, Bz, Ph or allyl) cyclize to the methyleneoxazolidinones 58 under the influence of silver cyanate or copper(I) chloride/triethylamine (94BCJ2838). 

In the last few years numerous reports have been published in the field of microwave-promoted aryl halide cyanation, utilizing nickel [71], palladium [72,73] and copper [74,75] catalysis. Even water [75] and ionic liquids [76] have proven useful as solvents in these processes. Srivastava and Collibee have exemplified a swift and dynamic procedure using polymer-supported triphenyl phosphine to enable easy subsequent removal through filtration [72]. As shown in Scheme 19, both bromides and iodides could be activated using palladium catalysis in DMF. Even without optimization of the individual reaction times, the overall process time involving simple filtration and extraction for compound isolation appears to be short. 

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