Halides, aryl, arylation cyanation

Aryl cyanates can be prepared by reaction of phenols with cyanogen halides in the presence of a base ArO + CICN ArOCN + CP. This reaction has also been applied to certain alkyl cyanates. ... 

The aromatic cyanates are of much more importance. If phenols are treated with cyano halides in such a way as to definitely prevent an excess of the corresponding phenolate, aryl cyanates can be isolated in up to quantitative yields. To achieve this, triethylamine is slowly added to an equimolar mixture of the phenol and the cyano halide in a nonprotic solvent, preferably acetone or n-pentane/diethyl ether (equation 27).Heteioaromatic hydroxy compounds can be treated in the same way. The method fails, however, if various electron-attracting substituents are present, as for instance with 2,4-dinitrophenol or polyhalophenols. ... 

Aryl cyanates and other stabilized cyanates can be acylated with various acyl halides to yield /V-acylchloroformimidatcs 15416 (cf. Houben-Weyl, Vol. E4, p 546). These compounds, which are surprisingly stable, easily react with amidincs to form 1,3,5-triazines 16.417 This reaction is believed to proceed via a nucleophilic substitution of the halide atom, followed by cyclization to the carbonyl carbon of the acyl group.417. In the case of phosgene (R2 = Cl), addition of amidines to the activated cyanates is not selective417,418 for formation of the 1,3,5-triazines. 

Lewis acid-catalyzed condensation of an aryl carbonitrile (2 equivs.) with an acyl halide (1 equiv.) is a well-established and popular route to 1,3,5-oxadiazinium salts (see Section 6.18.10.3.l.i). The carbonitrile can be replaced successfully by aryl cyanates, cyanamides, and alkylthiocyanates, and examples using carbamoyl chlorides rather than the acyl halide have also been reported. The 1,3,5-oxadiazinium salts are also accessible by cyclocondensation of A-acylchloroformamidines with cyanamides in the presence of stannic chloride (see Section 6.18.10.2.2.l.i) and by condensation of A A -disubstituted-ALacylthioureas (2 equivs.) with thionyl chloride or phosphorus pentachloride (see Section 6.18.10.2.2.i). 

The reaction of aryl cyanates with hydrogen chloride or hydrogen bromide in an inert solvent produces the haloformimidinium halides XL ( ). 

In the early 1960 s Grigat (1) and Martin (2) and Jenson (3) reported the synthesis of stable aryl cyanates. Grigat (1) prepared these new materials by reacting phenolic compounds with a cyanogen halide. 

Cyanation of aryl halides (aryl iodides and aryl bromides) was completed within 20 min using K [Fe(CN)g] as a cyanide source, water as the solvent and tetrabutylam-monium bromide (TBAB) in presence of palladium catalyst using microwave heating (Velmathi and Leadbeater, 2008). 

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]. 

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 synthesis of (hetero)aryl cyanides from (hetero)aryl halides via transition-metal catalysis is a very valuable reaction since a nitrile can be easily transformed into several other functional groups. Not until 2000 were the first examples on microwave-assisted cyanation reported in the literature. Alter-man and Hallberg found that 3-bromopyridine and 3-bromothiophene were... 

This is a problem that has been reported by several researchers in other cya-nation methods on heteroaromatic halides. (Hetero)aryl chlorides have also been tackled via in situ halogen exchange to (hetero)aryl bromides followed by sequential cyanation (Scheme 71). For this microwave-assisted process an equimolar amount of NiBr2 and a two-fold excess of NaCN were used. The only heteroaromatic chloride tested was 2-chloropyridine. Although the procedures described involve the use of significant amounts of nickel salts, a clear advantage is that the reactions can be performed in air. Moreover, the cyanat-ing reagents are easily removed since they are water soluble. 

In a related study, Srivastava and Collibee employed polymer-supported triphenyl-phosphine in palladium-catalyzed cyanations [142]. Commercially available resin-bound triphenylphosphine was admixed with palladium(II) acetate in N,N-dimethyl-formamide in order to generate the heterogeneous catalytic system. The mixture was stirred for 2 h under nitrogen atmosphere in a sealed microwave reaction vessel, to achieve complete formation of the active palladium-phosphine complex. The septum was then removed and equimolar amounts of zinc(II) cyanide and the requisite aryl halide were added. After purging with nitrogen and resealing, the vessel was transferred to the microwave reactor and irradiated at 140 °C for 30-50 min... 

An improvement of the palladium-catalyzed cyanation of aryl bromides, in which zinc cyanide was used as the cyanide source, was reported in the middle of the nineties [49], Typically, the conversion from halide to nitrile takes at least 5 h by this route and the subsequent cycloaddition to the tetrazole is known to require even longer reaction times. 

Schareina T, Zapf A, Beller M (2004a) Potassium hexacyanoferrate(II)—a new cyanating agent for the palladium-catalyzed cyanation of aryl halides. Chem Commun 1388-1389... 

The concept of CPTC has been applied in a large number of catalytic reactions such as reduction of allyl chlorides with HCOONa, carbonylation of aryl and allyl halides, allylation of aldehydes, cyanation of aryl halides etc.214 For example, Okano et a/.215 reduced l-chloro-2-nonene to afford 1-nonene and... 

The nickel-catalyzed transformation of aromatic halides into the corresponding nitriles by reaction with cyanide ions is reported. Both tris(triarylphosphine)nickel(0) complexes and tY2ins-chloro( aryl )bis( triarylphosphine )nickel(II) complexes catalyze the reaction. The influence of solvents, organophos-phines, and substituents on the aromatic nucleus on catalytic cyanation is studied. A mechanism of the catalytic process is suggested based on the study of stoichiometric cyanation of ti3ins-chloro(aryl)bis(triphenylphosphine)nickel-(II) complexes with NaCN and the oxidative addition reaction of Ni[P(C6H5)3]s with substituted aryl halides. 

Cyanation Catalyzed by trans-CHLORO ( aryl ) bis ( triphenylphos-phine) nickel (II) Complexes. In Table III cyanation of aryl halides catalyzed by the Ni(II) complexes obtained by reaction between aryl halides and Ni[P(C6H5)3]3 (Reaction 2) is shown. In general the trans-chloro (1-naphthyl) bis (triphenylphosphine) nickel (II) complex was used. Ortho substituted aryl halides were allowed to react in dimethylformamide... 

By using this source of cyanide ions the reaction occurred in a variety of solvents and at very mild conditions. For example in acetone it was possible to observe a rapid reaction even at 30 °C. A strong base, such as triethylamine, was necessary to induce the formation of cyanide ion (15). In the presence of weak bases such as pyridine, cyanation does not occur under the same reaction conditions. Ortho substituted aryl halides were... 

As reported before, the reaction can be carried out in ethanol by adding quickly a stoichiometric quantity of NaCN after the catalyst and aryl halide additions. In methanol or in dimethylformamide the catalytic cyanation occurs only if the sodium cyanide is added slowly. In benzene, always in the presence of NaCN, the reaction does not occur and complexes 1 can be isolated. 

Therefore it seems reasonable to assume that cyanation of aryl halides involves two fundamental processes oxidative addition of the tris(triphenylphosphine)nickel complex on the aromatic halide (Reaction 2) and cyanation of the arylnickel(II) complex 1 (Reaction 8). A further proof of the validity of this scheme is that both Ni[P(C6H5)3]3 and arylnickel (II) complexes 1 have an equal catalytic activity, these latter being intermediates of the catalytic process. Recent studies (22) on the influence of substituents on the aromatic halide in the oxidative addition reaction with Ni[P(C6H5)3]3 have given the results shown in Figure 4. 

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. 

Sundermeier, M. Zapf, A. Beller, M. A convenient procedure for the Pd-catalyzed cyanation of aryl halides. Angew. Chem. Int. Ed. 2003, 42, 1661-1664. 

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. 

The hydrocyanation of alkenes [1] has great potential in catalytic carbon-carbon bond-formation because the nitriles obtained can be converted into a variety of products [2]. Although the cyanation of aryl halides [3] and carbon-hetero double bonds (aldehydes, ketones, and imines) [4] is well studied, the hydrocyanation of alkenes has mainly focused on the DuPont adiponitrile process [5]. Adiponitrile is produced from butadiene in a three-step process via hydrocyanation, isomerization, and a second hydrocyanation step, as displayed in Figure 1. This process was developed in the 1970s with a monodentate phosphite-based zerovalent nickel catalyst [6],... 

Although isocyanates have been known for some time, the isomeric cy-anates were unknown until 1964. The latter were first prepared almost simultaneously by two different methods (1) thermolysis of 5-aryl- or 5-alkyloxy-l,2,3,4-thiatriazoles67 and (2) by reaction of phenols or alcohols with cyanogen halides.8 Since their synthesis, cyanates have ac-... 

The palladium-catalyzed reaction of aryl halides with cyanides to give cyanobenzenes takes place under relatively mild conditions compared to the conventional method using a stoichiometric amount of CuCN [74]. Thus, palladium catalysis has been often employed. Recently, a number of effective methods for the cyanation have been reported. The reaction of aryl iodides with NaCN under two-phase conditions [75] and those of aryl triflates [76, 77] and aryl chlorides [78] with Zn(CN)2 occur with good efficiency, while these are considered to proceed via mechanism B. 

Cyanation of aryl halides to form nitriles is generally robust unless catalyzed by Co, Ni or Pd complexes [167 —171], A useful catalytic mixture comprises NiBr2/Zn/ phosphine/KCN. The use of PPh3 is sufficient to achieve good conversion of chlorobenzene to benzonitrile. But for the more resistant o-dichlorobenzene and o-chlorobenzonitrile, dppf is reported to show better conversion and selectivity [172], The choice of phosphine is obviously crucial as P(o-Tol)3 and dppe are distinctly ineffective. The superiority of dppf over many other phosphines is remarkably evident in the cyanation of aryl triflates and halides when catalyzed by phosphine-doped Pd2(dba)3 [173]. 

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