Intramolecular heterocyclization

One-bond formation through (5+0) atoms intramolecular heterocyclization of pyrimidines having an -N-N-C appendage at Nl(3) and a leaving group at C4(6) (Scheme 6). 

It is assumed that at the initial stage, after benzimidazoline-2-thione has been added to compound 1, the resultant anion formed, then is deprotonated by triethylamine added to the resulting suspension. The ensuing intermediate undergoes intramolecular heterocyclization into compound 153. Using acetonitrile as a solvent is also essential because of its low ability to undergo proton transfer and the low solubility of benzimidazoline-2-thione in it. This combination of properties initially yields the kinetic product and then leads to activation of the second nucleophilic center. 

Addition of several lithium ester enolates to chiral 1-aminoalkyl choromethyl ketones gave the corresponding chlorohydrins which, when the solvent was completely evaporated to dryness at room temperature, underwent an intramolecular heterocyclization affording 3-hydroxyazetidinium salts 5 <02OL1299>. Azetidinium salts 5 were isolated in enantiomerically pure form, and with total or high diastereoselectivity. The degree of stereoselectivity was only moderately affected by the size of R1 in the a-amino-ketone and the substituents in the ester enolate. 

Double ring-closure comprising two-bond formation by intramolecular heterocyclization of (9+0) atoms open structures consisting of five carbons and four nitrogens (C5N4) (Scheme 32). 

A versatile synthesis of pyrazoles from benzophenone hydrazones was demonstrated with a variety of 1,3-bifunctional substrates under acidic conditions <2002TL2171>. Hydrazones 668 and 671, prepared from palladium-catalyzed heteroaryl halides with benzophenone hydrazone, reacted with 1,3-bifunctional substrates 669 and 672 under acidic conditions to yield pyrazoles 670 and 673, respectively (Equations 139 and 140) <2004TL5935>. Enolates of a-chloro-/3-oxoaldehydes react with arylhydrazines in the presence of acetic acid or / -oxo-a-chlorenamines react with arylhydrazines to produce osazones of carbonyl-substituted glyoxals, which under conditions of acid catalysis undergo intramolecular heterocyclization to the corresponding functionalized pyrazoles <1998CHE167>. 

The compounds 55-60 have all been prepared, albeit in low yields (8-26%), from the reaction of Sn(NMe2)2 with the appropriate primary amine, under conditions which produce cubanes for non-heterocyclic containing amines. Thus, the formation of the double-cubane structural motif presumably arises from the nature of the heterocyclic substituents on the imido nitrogen centers. Inspection of the solid-state structures of these compounds revealed the presence of short intramolecular heterocyclic N- -Sn contacts, ranging from 2.812(4) to 3.188(6) A, which may play a role in the formation of the double cubanes. The likely formation of double-cubane clusters, which do not contain heterocyclic imido substituents, by metathetical reactions of two equivalents of 53 or 54 with main-group or transition-metal tetrahalides has not yet been investigated. 

Intramolecular heterocyclization in polyacrylonitrile 86UK62. a-Isocyano acetates, synthesis of N-heterocycles from 85YGK764. Isonitrosotosyl malonates in synthesis of N-heterocycles 80H(14)1581. Lactams, regioselective formation from bridged bicyclic ketones 81T1283. Malononitrile derivatives, synthesis of N-heterocycles condensed from ... 

The synthesis of this type of compound was achieved by nucleophilic attack of the nitrogen of the C-3 hydrazone residue on C-6 of 65c when it carries a leaving substituent such as a sulfonyloxy group or a bromine atom. This intramolecular heterocyclization process was achieved by the action of sodium iodide in acetone or by the action of acetic anhydride on the mono-O-p-toluene sulfonate to give 111 and 114, respectively (82MI5) (Scheme 28). The spectral data confirmed the assigned structure. 

Likewise, interaction of terminal alkynes with 20 in refluxing acetonitrile in the presence of toluenesulfonic acid gives the intramolecular heterocyclic alkynyliodonium salts 21 [Eq. (11)] [33]. A wide range of the alkyl- and phenyl-substituted congeners 21 of these intramolecular analogs of the acyclic iodonium tosylates, 9, are obtained in 26-70% isolated yields. 

Aryl-2-(carboxymethyl)(or carboxyethyl)thiazolo[3, 4 2,3]-l,2,4-triazolo[5,4-3]-l,3,3-thiadiazines 234 are obtained from 2-aryl-3-thioureido-4-thiazolidinones 235, which are formed by the addition-condensation of aldehyde thiosemi-carbazones 237 and mercaptoacetic acid. Compounds 235 undergo chemoselective intramolecular heterocyclizations to 5-aryl-2-mercapto-l,5-dihydrothiazolo[3,4- ]-l,2,4-triazoles 236, which in turn undergo condensation with a-amino acids to yield 1,3,5-thiadiazines 234 (Scheme 44) <1994JFA811>. 

Indoles or heterocycles containing an indole skeleton were the first products to be prepared by intramolecular heterocyclic Mizoroki-Heckreaction. In 1977, the first intramolecular Mizoroki-Heck reaction was reported by Mori et al. [7], who prepared indole 3 by cyclization of (Fl-methyl 4-(N-(2-bromophenyl)acetamido)but-2-enoate (1) in the presence of palladium acetate, triphenylphosphine and iVA/ A A -tetramethylethylenediamine (Scheme 6.4). 

Scheme 6.14 Cascade of two intramolecular heterocyclic-forming Mizoroki-Heck reactions with anion capture.

A large number of enantioselective domino Michael/intramolecular heterocyclization reactions have been successfully developed in the last years, using three... 

Scheme 13 Intramolecular heterocyclization route to 3-aryl-4(31f)-quinazolinones [ 189]...

Pyrido[l,2-a]benzimidazoles as a kind of fused benzimidazole were prepared as well. In 2006, Ila and co-workers developed a new high-yielding route for benzimidazo[l,2-a]quinolines via palladium-catalyzed intramolecular heterocyclization of readily accessible 2-(2 -bromoanilino)quinolines. ... 

It was found that compounds 1025 i.e. 1028) react with p-dicarbonyl compounds to give pyridazine derivatives 1029 (Scheme 219) [620], In this case, inter-molecular diaza-Wittig reaction occurred, followed by intramolecular heterocyclization. The reaction was sensitive to steric factors in case of p-diketone possessing bulky iert-butyl group, 1029 was isolated in low yield (9 %). 

The first parallel solid-phase 1,3,5-triazino-annulation S5mthesis has been achieved by Hoesl et al. [28]. Aza-Wittig reaction of an iminophosphorane generated in situ from a resin-bound 2-aminobenzimidazole (under Mitsunobu conditions) resulted in the formation of a highly reactive carbodiimide intermediate, which subsequently underwent intramolecular heterocyclization to afford the corresponding triazinobenzimidazoles (Scheme 7). 

At the same time, control experiments have shown that compounds 13a,b do not undergo intramolecular heterocyclization in CH2CI2 and LiC104 - MeN02 and hence the products 14a,b are formed in the course of the Ade reaction. 

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