Ethers cyanation

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]. 

Alkylation. Ben2otrifluoride can also be alkylated, eg, chloromethyl methyl ether—chlorosulfonic acid forms 3-(trifluoromethyl)ben2yl chloride [705-29-3] (303,304), which can also be made from / -xylene by a chlorination—fluorination sequence (305). Exchange cyanation of this product in the presence of phase-transfer catalysts gives 3-(trifluoromethylphenyl)acetonitrile [2338-76-3] (304,305), a key intermediate to the herbicides flurtamone... 

Other functional groups that are easily differentiated are cyanide (5c =110-120) from isocyanide (5c = 135- 150), thiocyanate (5c =110-120) from isothiocyanate (5c = 125 - 140), cyanate (5c = 105- 120) from isocyanate (5c = 120- 135) and aliphatic C atoms which are bonded to different heteroatoms or substituents (Table 2.2). Thus ether-methoxy generally appears between 5c = 55 and 62, ester-methoxy at 5c = 52 N-methyl generally lies between 5c = 30 and 45 and. S-methyl at about 5c = 25. However, methyl signals at 5c = 20 may also arise from methyl groups attached to C=X or C=C double bonds, e.g. as in acetyl, C//j-CO-. 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

A typical phase transfer catalytic reaction of the liquid/liquid type is the cyanation of an alkyl halide in an organic phase using sodium or potassium cyanide in an aqueous phase. When these phases are stirred and heated together very little reaction occurs. However, addition of a small amount of crown ether (or cryptand) results in the reaction occurring to yield the required nitrile. The crown serves to transport the cyanide ion, as its ion pair with the complexed potassium cation, into the organic phase allowing the reaction to proceed. 

A" 0-Butenolide, 46, 22 /-Butyl alcohol, in synthesis of phenyl /-butyl ether, 45, 89 reaction with sodium cyanate and trifluoroacetic acid, 48, 32 /-Butyl azidoacctatc, 46, 47 hydrogenation of, 45, 47 /-Butyl carbamate, 48,32 /-Butyl chloroacetate, reaction with sodium azide, 45, 47 /ra S-4-/-BuTYI,CYCLOHEXANOL, 47,16... 

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,... 

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]. 

The double process of cyanation/transcyanation of co-bromoaldehydes and racemic cyanohydrins as a source of HCN is a really interesting process (Scheme 10.25). Thus, using this reaction it is possible to obtain optically active (S)-ketone- and (R)-aldehyde-cyanohydrins in one pot [55], The reaction is carried out in diisopropyl ether using a crude extract of almond containing (R)-oxynitrilase as biocatalyst. The optically active (a-bromocyanohydrins prepared by this method is used as starting materials for the synthesis of valuable compounds such as... 

---