Cyanation conditions

It has been shown52 that under similar conditions reduction of the nitrile groups in cellulose ethyl cyanate and of those in the copolymer of vinylidene cyanide with vinyl acetate, proceed simultaneously in two directions with the formation of aldehyde and amine groups. g+ g ... 

Novolac hydroxyl groups reacted with cyanogen bromide under basic conditions to produce cyanate ester resins (Fig. 7.41).105,106 Cyanate esters can thermally crosslink to form void-free networks, wherein at least some triazine rings form. The resultant networks possess high s, high char yields at 900°C, and high decomposition temperatures.105... 

These modified Rosenmund von Braun reaction conditions were also used by Gopalsamy et al. for the rapid cyanation of the 1,3,4,9-tetrahydropyrano-[3,4-fc]indole skeleton while searching for potent and selective Hepatitis C virus polymerase inhibitors (Scheme 74) [84]. 

Nickel-catalyzed carbonylation of a-ketoalkynes has also been reported by Arzoumanian et al. under phase-transfer conditions.94 The carbonylation gave either furanone or unsaturated carboxylic acids depending on the substituents of substrates (Eq. 4.53). A similar reaction, nickel-catalyzed cyanation of a-ketoalkynes with KCN in water, was also reported to afford unsaturated hydroxylactams (Eq. 4.54).95... 

It is not clear whether the conditions used in the above experiments correspond to those present on the young Earth. Cyanate has been detected in cosmic nebulae (Yamagata, 1999), while water-soluble phosphates and diphosphates can be formed during volcanic activity, as Yamagata showed as early as 1991 (see Sect. 4.7.3). 

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). 

A novel route to synthesize l,3 -triazine-2,4(l//,3//)-diones through the desulfurization of thiocarboamides, such as 1,3-disubstituted 2-thioureas, trisubstituted thioureas and N-substituted thioamides by silver cyanate has been reported <00H(53)929>. Treatment of urazole 23 with one equivalent of sodium hydride under anhydrous conditions, followed by addition of dimethyl sulfate, leads to l,3,5-triazine-2,4-dione 24 in 80% yield . 

A cascade process involving a Ni-catalysed coupling, carbonylation, cyanation and heterocyclisation results in the rapid, efficient conversion of propynyl halides and alcohols into 5-cyanopyran-2-ones in aqueous conditions (Scheme 37) <00JCS(P1)1493>. 

Yamamura and Murahashi (1977) have studied the crown ether-catalysed cyanation of vinyl halides under solid—liquid phase-transfer conditions (20). The reaction of /rans-/ -bromostyrene [140] with sodium cyanide in benzene,... 

Scheme 5.5 The products of a simple nucleophilic substitution reaction is dependent on reaction conditions, and a PTC is essential for successful cyanation in water...

Autoxidation of secondary acetonitriles under phase-transfer catalytic conditions [2] avoids the use of hazardous and/or expensive materials required for the classical conversion of the nitriles into ketones. In the course of C-alkylation of secondary acetonitriles (see Chapter 6), it had been noted that oxidative cleavage of the nitrile group frequently occurred (Scheme 10.7) [3]. In both cases, oxidation of the anionic intermediate presumably proceeds via the peroxy derivative with the extrusion of the cyanate ion [2], Advantage of the direct oxidation reaction has been made in the synthesis of aryl ketones [3], particularly of benzoylheteroarenes. The cyanomethylheteroarenes, obtained by a photochemically induced reaction of halo-heteroarenes with phenylacetonitrile, are oxidized by air under the basic conditions. Oxidative coupling of bromoacetonitriles under basic catalytic conditions has been also observed (see Chapter 6). 

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]. 

Numerous biocatalytic routes to this challenging intermediate have been reported. " For example. Fox et al. have recently developed an efficient regioselective cyanation starting from low-cost epichlorohydrin (Scheme 1.26). Initial experiments found that halohydrin dehydrogenase from Agrobacterium radiobacter expressed in E. coli produced the desired product, but inefficiently. To meet the projected cost requirements for economic viability, the product needed to be produced at 100 g L with complete conversion and a 4000-fold increase in volumetric productivity. The biocatalyst needed to function under neutral conditions to avoid by-product formation, which causes downstream processing issues. 

---