Addition to the Cyano Group

In conclusion, free radical intramolecular addition to the cyano group, although not much studied, is a facile process. In all the cases reported, addi- 

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The reaction depicted in equation 43 between a nitrile and a lithium amide takes place as a 1,2-addition to the cyano group. The product crystallizes as a dimer (236) in which the lithium atoms are solvated by nitrile molecules and differently bonded to the amidine moieties, as shown by XRD analysis. Low-temperature H NMR spectrum in solution points to uniform chemical environments for both the aryl groups and for the Me—Si groups, and to rapid rearrangement of the Li—N coordination structures. Acidolysis of the dimer in solution yields the corresponding amidine (237) . The crystal structure of the THF-solvated analog of 236 shows dissimilar N—Li bond lengths for the two Li atoms... 

Various mechanisms can be envisaged for the conversion of substituted acetonitriles into dithiazolium salt 145, yet no firm evidence has been given. The first step could be the chlorination of acetonitrile by sulfur monochloiide, as demonstrated for acetonitrile itself (1985CB1632) and for phenylacetonitrile (1939ZOK1329). This could be followed by sulfur monochloride addition to the cyano group, cyclization and ionization (Scheme 75). 

The transformation of 5-nitropyrimidine into pyridine derivatives by the reaction of carbanions bearing, in addition to the cyano group, a suitable function R which is cyclizable with the 2-amino substituent of the new pyridine leads to pyrido[2,3-[Pg.132]

Meyers, A.L, Siicar,J.C. Addition to the cyano group to heterocycles. Aus Rappoport,Z. The chemistry of the cyano group. London Interscimx e Publ. 1970. 

Heteroarenes have been photochemically functionalized by PET reactions forming new C—C bonds both in an inter- and intramolecular fashion via a similar mechanism [46]. The heteroarenes could serve both as electron donor (e.g. pyrroles or indoles) or electron acceptor (e.g. cyanopyridines or cyanopyrazines). Again, fragmentation of the radical cation, coupled with the radical anion and loss of the anion, led to overall ipso-substitution. In addition to the cyano group, halides could also function as leaving groups, such that in some cases an attack at an unsubstituted position took place [46],... 

Johns and Willing have reported an interesting example of polycyclization involving addition to a cyano group (Scheme 155). The reaction of the diallyl amine 444 with AIBN gives the ketone 448. This would result from addition of the cyanoisopropyl radical to 444 followed by Cy5 cyclization of 445 in a Cy5/Cy6 case to the pyrrolidine radical 446. This radical would cyclize to 447 by Cy6 intramolecular addition to the cyano group in a Cy6/Cy7 case and, finally, the intermediate imine would be hydrolyzed to the ketone 448. 

Tetracyanobutanal acetal (216) (readily obtained from tetracyanoethylene, ethyl vinyl ether, and ethanol) has been reported to be converted into 2-aminopyridine derivative (219) in the presence of pyridine. On the basis of several experiments, the proposed mechanism involves the Michael reaction of (216) via (217) with diene (218), generated by the elimination of hydrogen cyanide and ethanol from (216), followed by double intramolecular nucleophilic additions to the cyano groups. ... 

Formation of 39 can be interpreted by condensation of both reactants to give the imine 41, followed by intramolecular amine addition to the cyano group ( 42) and concluded by tautomerization ( 39). 

Pyrazole formation is likely to occur via hydrazone formation (—>20) and cyclization by intramolecular NH-addition to the cyano group (—>21) concluded by tautomerization —>19). A solid-phase-catalyzed version (montmoriUonite K-10) was reported [436] as well as the use of acetylhydrazine for minimizing side reactions and removal of the acetyl group by N-methylpiperazine [437]. 

It is believed (54IZV47 72JPR353) that in the first stage the intermediate 282 is formed due to the addition of the CH acid to the enamine moiety with subsequent elimination of amine. The enol form of the intermediate 282 undergoes cyclization in two fashions, depending on the nature of substituent X. In the case of the ester (X = OMe) the attack is directed to the cyano group to form substituted 3-methoxycarbonyl-I//-pyridin-2-one (283) or its tautomer (2-hydroxy-3-methoxycarbonylpyridine). With the amide (X = NH2) intramolecular condensation leads to 3-cyano-l//-pyridin-2-one and its hydroxy tautomer (284). 

S909). First, an addition of the cyano group takes place to give intermediate 127, in which nucleophilic substitution of aliphatic nitro group provides the final product 128 (Scheme 20). 

Enantiopure 3-phenyl-2-cyanoazetidines (S)-238 and (K)-238, which are epimeric at C2, are prepared in high yields from (K)-phenylglycinol. A one-pot sequence, including addition of organohthium or allyhnagne-sium bromide to the cyano group and in situ reduction of the resulting imine with sodium borohydride, allowed for the preparation of 2-(l-aminoalkyl)azetidines, which were then protected as N-Boc derivatives (R,S)-239 and (S,it)-239 [112] (Scheme 36). Complete anti diastereoselectivity (dr more than 95 5 by NMR) was observed in both cases. The same sequence... 

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Reaction of the malononitrile-derived diazene 275 with active methylene compounds proceeds via addition to a cyano group followed by intramolecular hydrazide or thiohydrazide formation, pyridazin-3(2//)-ones and thio analogs 276 are respectively produced (Equation 70) <1999JCM8>. 

It is possible to introduce a heterocyclic ring as a substituent by addition to a cyano group. Adding ethylenediamine to 64 in the presence of a trace amount of CS2 allows the formation of 65 in good yield (Equation 26) <1997PHA500>. 

Further transformations of a-alkyl-3-oxazolidineacetonitriles are possible. Addition of methyllithium to the cyano group followed by acid hydrolysis gave a morpholine derivative, from which a /i-amino alcohol was obtained as a diastereomeric mixture (d.r. 80 20)69. 

Primary aliphatic amines give two products when substitution of two cyano groups is attempted. One is the normal 2,6-disubstitution product and the other is the result of one substitution of, and one addition to, a cyano group. 

The apparently quite broad structural requirements for anticonvulsant activity, noted earlier in this chapter, extend to yet another class of five-membered heterocycles that include an imide function. Imidazo-2,4-diones, better known as hydan-toins, have comprised some of the most widely used drugs for treating severe motor and psychomotor epileptic seizures. The general reaction used to prepare this heterocyclic system involves the treatment of a carbonyl compound with ammonium carbonate and potassium cyanide. The first step in the complex sequence can be visualized as the addition of the elements of ammonia and hydrogen cyanide to give an a-aminonitrile (88-2). Addition of ammonia to the cyano group would then lead to an amidine (88-3). Carbon dioxide or carbonate ion present in the reaction... 

The preparation of a pair of iminohydantoins invokes the addition of amide nitrogen to a cyano group for formation of the imidazole ring. The products exhibit unexpectedly quite different biological activities. Reaction of the cyanamide (92-1) from para-chloroaniline and cyanogen bromide with A-methylchloroacetamide (92-2) can be visualized to lead initially to the alkylation product (92-3). Cyclization by addition to the nitrile group then affords clazolamine (92-4) [98], a compound described as a diuretic. 

The use of the y-(trimethylsiloxy)nitrile derivatives (190) as a route to 1,4-bifunctional units is exemplified in a convenient synthesis of jasmonoid compounds. The addition of the Grignard reagent to the cyano group as the homologation step results in the keto alcohol (191) after subsequent hydration. The y-ketocarboxylic add (192) obtained from the... 

A correlation between free enthalpy of electron transfer and mode of the photoreaction was also constructed for addition of alkenes to benzonitrile. Four areas could be differentiated Full electron transfer, leading to substitution, is only observed if AG < 0 eV cycloaddition to the cyano group occurs if 0 < AG < 0.4 eV. All olefins for which AG > 0.4 eV preferentially undergo cycloaddition to the aromatic ring, ortho cycloaddition if AG < 1.7 eV and meta cycloaddition if AG > 1.7 eV. 

The treatment of iminodithiazole 96 with alcohol and a base gives quinazoline-2-carbonitriles 97 in good yield (Equation 18). A reasonable mechanism would appear to be addition of alkoxide ion to the cyano group and cyclization with the attack on C-5 of 1,2,3-dithiazole ring followed by elimination of S2 and HCI <1998T6475>. 

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