Aromatic nitrile cyclization

Diazadienes 314 (R2 = Ph) afforded, in the same way, good yields of bis-trifluoromethyl dihydroquinazolines 335, as reported by Burger and Penninger (Scheme 74). However, N-unsubstituted heterodienes 314 (R2 = H) yielded upon heating with aromatic nitriles symmetrical triazine derivatives 336 through a [4 + 2] cycloaddition (78S524). Muchowski and co-workers have employed the related 2-trichloromethyl-4-dimethyl-amino-1,3-diaza-l, 3-butadienes 337 for synthesizing 2-trichloromethylpyr-imidines 338 in 38-98% yield by cyclization with electron-deficient acetylenes moreover, triazine 339 was obtained in 80% yield in the reaction of... 

The reaction of 1-lithiobuta-l,3-dienes with aromatic nitriles produced substituted pyridines, pyrroles, and/or linear butadienylimines in good to excellent yields. The competition between 5-exo and 6-endo cyclization is responsible for the formation of either pyrroles or pyridines.2... 

The base-catalysed intermolecular condensation of nitriles of the type RCH2CN is one of the oldest known methods for the preparation of -enaminonitriles, and in the case of simple self-condensation it leads to aliphatic analogues of the cyclic ji-ena.-minonitriles formed in the classical Thorpe-Ziegler cyclization. For example, the base-catalysed dimerization of acetonitrile with sodium gives 3-amino-crotononiirile Cross-condensation between acetonitrile and aromatic nitriles or higher aliphatic nitriles leads to substituted j8-enaminonitriles 156 (R = alkyl, aryl). 

Another electrophilic reaction of the double salt is with carbonyl compounds on addition to benzophenone, the appropriate hydroxyphenylhydrazone 50 is obtained , When the electrophile is an aroyl chloride, 4-acetylpyrazole 51 is obtained whereas reaction with an cster or with an aromatic nitrile gives pyrazole derivatives by addition, followed by an intramolecular cyclization (equation 29). 

The isolable potassium salts (74) (available from the nucleophilic addition of 4-amino-l-methyl-3-methylthio-l -l,2,4-triazole-5(4//)-thiones (73) to aromatic nitriles in the presence of base) upon acidification with hydrochloric acid cyclize to give 7/7-[l,2,4]triazolo[4,3-fc][l,2,4]triazole-3(2//)-thiones (75) (Scheme 5) <85BCJ735>. 

Lee and Hong" described the first direct synthesis of 2-alkyl-5-aryloxazoles 206 from aromatic a-methyl ketones (Scheme 1.57). They used thallium(III)triflate generated in sim to convert a ketone to the a-ketotriflate 204. Reaction of 204 with a nitrile most likely produces a nitrilium salt 205, as proposed by Meyers and Sicar, which subsequently cyclizes to 206. The reaction works well for aliphatic nitriles regardless of steric hindrance. Aromatic nitriles are not as useful,... 

A second new route to DPP Pigments was developed and published 1983 In this route, succinic ester is condensed in a pseudo-Stobbe condensation with an aromatic nitrile in the presence of strong base to afford the desired DPP in good yield (Stdieme 11—4). Mechanistically, the formation of a DPP unit from succinic esters is believed to proceed along the pathway shown in Scheme 11—4. TTie initially formed enaminoesters 5C/5D cyclize to the pyrrolinone esters 6B, which further react under basic conditions with another benzonitrile. Subsequent ring closure affords the DPP 2. 

LiCCl2CH=CH2 to an a-methylene-ketone, followed by cyclization of the chloropentadienyl cation (22) and hydrolysis. 5-Methylisoxazole is a precursor of the dianion (23), which, amongst other useful reactions, gives aminopyridones with aromatic nitriles. 

Very recently, the cyclization of aromatic nitriles with alkenes was also explored. A variety of 3-methyleneisoindolin-l-ones were formed in high Z-stereoselective manner via in situ generated cationic Ru(II) catalyst (Eq. (7.51)) [61]. The high Z-stereoselectivity was attributed to the intramolecular hydrogen bonding. 

Scheme 7.12 Proposed mechanism for ruthenium-catalyzed oxidative alkenylation and cyclization of aromatic nitriles.

The other main reaction in this class is the Dieckmann-type cyclization of the intermediates (163) from 4(6)-halo-5-ethoxycarbonylpyrimidines with AC-substituted /3-alanine esters and nitriles, and related compounds, to give 5,6,7,8-tetrahydro-5-oxopyrido[2,3-[Pg.221]

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

Cyclization is a key reaction in the production of carbon fibers from polyacrylonitrile (PAN) (acrylic fiber see Sec. 3-14d-2). The acrylic fiber used for this purpose usually contains no more than 0.5-5% comonomer (usually methyl acrylate or methacrylate or methacrylic acid). Highly drawn (oriented) fibers are subjected to successive thermal treatments—initially 200-300°C in air followed by 1200-2000°C in nitrogen [Riggs, 1985]. PAN undergoes cyclization via polymerization through the nitrile groups to form a ladder structure (XXVII). Further reaction results in aromatization to the polyquinizarine structure (XXVIII)... 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. 

Cyclizations with perfluoroacylating agents seem to be quite general for the synthesis of 5(2i7)-oxazolones with aromatic substituents directly bonded to the heterocyclic ring. For example, perfluoroacylation of a solution of an arylgly-cine containing a phosphorus trihalide affords 4-aryl-2-(perfluoroalkyl)-5(2//)-oxazolones (Table 7.1, Fig. 12) Similar results were obtained when amino nitriles were used as starting materials. ... 

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