ARYL NITRILE FORMATION

Kurabayashi and Grundmann have reported the preparation of the 1,2,4-oxadiazoles (34) from 1,3,5-triazine and aryl nitrile oxides in the presence of boron trifluoride. The mechanism has not been fully elucidated, but it is most likely that the initial stage is the formation of the complex (33) (78BCJ1484). 

Subsequently, it was shown that the reaction was catalyzed by base (48M(79)106). Dicyandiamide reacts with nitriles (the most valuable method), amidines, cyanamides, ammonia, cyanates, thiocyanates, carboxylic acids and anhydrides to yield 1,3,5-triazines (Table 13). This synthetic route has been reviewed thoroughly several times (59HC(13)1, p. 219,61MI22000, p. 650, 73ZC408). The base-catalyzed reaction of dicyandiamide with alkyl or aryl nitriles (Scheme 65) proceeds via the imino ether anion and the rate determining step is solvent dependent. In DMSO the formation of the imino ether is rate determining, but in 2-methoxyethanol the reaction between the anion and dicyandiamide controls the rate (66T157). 

Cationic methylplatinum(II)-nitrile complexes of the type m is-PtMeL2(NCR)+X have been isolated by the reaction of //vms-PtMeClL2, where L = dimethylphenylphosphine or trimethyl-arsine, with an aryl nitrile and AgX, where X = BF4, PF. Use of pentafluorobenzonitrile and 2,3,5,6-tetrafluorotetraphthalonitrile in alcohol has led to the synthesis of a series of imino ether complexes. A mechanism for imino ether formation, involving nucleophilic attack by an alcohol at a coordinated nitrile, is suggested and the course of the reaction is shown to be dependent not only on the alcohol but also on the size of the anion used.110... 

Dihydrooxazoles 275 can be made by the condensation of aryl nitriles with amino alcohols catalyzed by Bi(iii) salts <2005SL2747> or acidic clay <1998TL459> in good yields (Bi salts - 70-92% kaolinitic clay -56-96%) (Equation 16). The use of Bi salts is only applicable to the formation of 2-aryloxazolines while the latter method works well for both aromatic as well as aliphatic substrates. The conversion of carboxylic esters to 2-oxazolines 276 in good (44-82%) yields with lanthanide chloride as catalyst <1997TL7019> has also been described (Equation 17). 

Triflic anhydride was found to be efficient for the cyclotrimerization of dialkylcyanamides 166 under mild conditions. The same reaction can be applied to aryl nitriles and thiocyanates. The reaction involves the formation of the bistrifluoroisourea intermediates 167, which react quickly with two molecules of cyanamide to afford the triazines 168 (Scheme 25) <2004S503>. 

A standard condition has been optimized for this reaction, in which the aryl amine is diazotized in 10 times its amount of acetic acid, followed by the addition of one equivalent of cuprous halide in hydrohalic acid. Under these conditions, the acetate salt of aryl amine is relatively soluble, and less froth and tarry material are formed during diazo transformation. In addition, chlorination, bromination, and iodonation of p-haloaniline to dihalobenzenes under such standard conditions give almost comparable average yields. Other modifications of this reaction include the formation of phenyl selenocyanate by the reaction with potassium selenocyanate, and aryl nitrile by the reaction with nickel cyanide. Moreover, this reaction has been extended to the preparation of phenyl thiocyanate, phenyl isothiocyanate and aromatic sulfonyl chloride. ... 

The exceptional strength of the metal-cyanide linkage makes it challenging to develop catalytic processes that involve excess CN" as reagent. The Pd-catalyzed cyanation of aryl halides discussed in Chapter 19 to form aryl nitriles initially suffered from the formation of catalytically inactive cyanide complexes containing multiple CN" ligands the reaction has been improved by the use of ZnfCN) or Kj[Fe(CN)J as the CN" source. ... 

PROBLEM 12.54 Although simple alkyl and aryl nitriles are poor dienophiles, nitriles substituted with electron-withdrawing groups are more reactive. Provide mechanisms for the formations of the two products in the following reaction ... 

Tetrazoles. Aryl nitriles and alkyl nitriles are converted into the corresponding tetrazoles in the presence of dibutyltin oxide or trimethylaluminum in moderate to good yields. Amides or thioamides also react with TMSA to form tetrazoles. Reaction of a,/3-unsaturated ketones with TMSA can be catalyzed by TMSOTf in dichloromethane. A tandem strategy for fused tetra-zole formation has also been reported a [3-1-2] cycloaddition between a nitrile and TMSA in presence of dibutyltin oxide is followed by an intramolecular allylation to form a fused tetrazole in 60-82% yields. 

Very few examples were described in this class and the formation of the aryl-silicon bond was obtained analogously to the alkylation of aryl nitriles presented in Section 4.3.3 by ipso-substitution reaction induced by an initial electron transfer process. Thus, tetracyanobenzene in the presence of hexamethyldisilane was in part silylated... 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

While there is clear evidence for complex formation between certain electron donor and electron acceptor monomers, the evidence for participation of such complexes in copolymerization is often less compelling. One of the most studied systems is S-.V1 Al I copolymerization/8 75 However, the models have been applied to many copolymerizations of donor-acceptor pairs. Acceptor monomers have substituents such as carboxy, anhydride, ester, amide, imide or nitrile on the double bond. Donor monomers have substituents such as alkyl, vinyl, aryl, ether, sulfide and silane. A partial list of donor and acceptor monomers is provided in Table 7.6.65.-... 

Formation of mixtures of the above type, which is common with internal olefins, do not occur with many functionalized alkenes. Thus, tertiary cinnamates and cinnamides undergo cycloadditions with benzonitrile oxides to give the 5-Ph and 4-Ph regioisomers in a 25-30 75-70 ratio. This result is in contrast to that obtained when methyl cinnamate was used as the dipolarophile (177). 1,3-Dipolar cycloaddition of nitrile oxides to ethyl o -hydroxycinnamate proceeds regiose-lectively to afford the corresponding ethyl fra s-3-aryl-4,5-dihydro-5-(2-hydro-xyphenyl)-4-isoxazolecarboxylates 36 (178). Reaction of 4-[( )-(2-ethoxycarbo-nylvinyl)] coumarin with acetonitrile oxide gives 37 (R = Me) and 38 in 73% and 3% yields, respectively, while reaction of the same dipolarophile with 4-methoxy-benzonitrile oxide affords only 37 (R = 4-MeOCr>H4) (85%) (179). 

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