Aryl-1,6-naphthyridines reactions

Bismuth(lll) chloride catalyzes the intramolecular hetero-Diels-Alder reaction of aldimines, generated in situ from aromatic amines and the A -allyl derivative of o-aminobenzaldehyde, in acetonitrile at reflux to generate [l,6]naphthyridine derivatives <2002TL1573>. The hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propeneni-triles and enol ethers yields 2-alkoxy, 6-diaryl-3,4-dihydro-2//-pyran-5-carbonitriles (Scheme 29) <1997M1157>. 

This chapter covers information on the preparation, physical properties, and reactions of 1,5-naphyhyridine and its C-alkyl, C-aryl, /V-alkyl, and /V-aryl derivatives as well as their respective ring-reduced analogs. In addition, it includes methods for introducing alkyl or aryl groups (substituted or otherwise) into 1,5-naphthyridines already bearing substituents and the reactions specific to the alkyl or aryl groups in such compounds. For simplicity, the term alkyl-l,5-naphthyridine in this chapter is intended to include alkyl-, alkenyl-, alkynyl-, aralkyl-, and cycloalkyl-1,5-naphthyridines likewise, aryl-l,5-naphthyridine includes both aryl-and heteroaryl-1,5-naphthyridines. 

Although alkyl and aryl groups attached to a heterocyclic nucleus can undergo a wide variety of reactions and do have significant steric and electronic effects on adjacent substituents, little such data on 1,5-naphthyridines can be found in the literature. 

Only reactions specific to the alkyl or aryl groups in such 1,5-naphthyridines are illustrated in the following examples. 

This section covers the insertion of alkyl or aryl groups into existing 1,6-naphthyridines and the reactions specific to the alkyl or aryl groups therein The HNMR spectra of C-methyl groups and the 13CNMR spectra of A-methyl groups attached to 1,6-naphthyridine have been examined in some detail 964,1319... 

The reported reactions of the alkyl- and aryl-1,6-naphthyridines are illustrated by the following examples. 

This section covers the insertion of alkyl/aryl groups into existing 1,7-naphthyr-idines and the reactions specific to such groups attached to 1,7-naphthyridines. 

There appear to be no reported reactions that are specific to C-alkyl/aryl groups attached to 1,7-naphthyridines, but the effect of methiodide formation on the 13CNMR spectrum of 1,7-naphthyridine has been studied by comparison with similar treatment of analogous substrtates.1319 In addition, several (V-debenzylations from hydro-1,7-naphthyridines have been recorded see the following examples. 

Isocyanates have provided one carbon atom in transformations of the general type (296) - (290). Thus, azide (343) reacts with triphenylphosphine in a Staudinger reaction giving phosphorane (344) which is then treated with isocyanates (RNCO R = benzyl or aryl) giving naphthyridines (346) (50-59% yield) via the carbodiimide (345). The cyclization (345)->(346) occurred in toluene at 160°C (92T4601). Azide (347) undergoes a similar sequence of reactions yielding a 1 1 mixture of isomeric naphthyridines (348) and (349) (44—47% yield). 

Methoxybenzo[c]-2,7-naphthyridine [CuO was used as an additive for the reaction between a heteroaryltin and aryl bromide] [72]. 

Direct arylation of methyl imidazole with 2,7-dichloronaphthyridine leads to a potentially tetradentate and practically tridentate bis-carbene ligand on a naphthyridine scaffold [363]. Reaction of the bis-imidazolium salt with silver(l) oxide in the usual way yields a linear trinuclear silver carbene complex with this tris-bridging hgand (see Figure 3.115). 

In the past year, reviews on 1,8-naphthyridines, perimidines, polyazaphen-anthrenes, 3-azabicyclo[3.3.1]nonanes, and 1,2- and 2,1-benzothiazines have appeared. Reviews on specialist aspects of pyridine chemistry are devoted to the reactions of newly available pyridines, a,a -disubstituted pyridines, the reactions of pyridines with nucleophiles, the electrochemistry of IjT-disubstituted 4,4 -bipyridinium ions (the viologens such as paraquat), dihydropyridines, and 4-aryl-dihydropyridines (a new class of calcium antagonists). Reviews have been published on the cyclization of oximes and amides to quinolines and isoquinolines, quinoline- and isoquinoline-diones, benzo[fl ]- and benzo[c]-quinolizinium ions, azachrysene preparation, quinazolines with plant-growth-regulating and biocidal activities, quinazolines in pharmaceutical research, isotopic hydrogen exchange in... 

A route in which a synthon for such a dialdehyde is central depends on ortho lithiation of an aryl bromide for conversion to ortho bromoaryl aldehyde, then palladium-catalysed replacement of the halide with an alkyne, subsequent reaction with ammonia producing the isoquinoline. The sequence below shows how this type of approach can be used to produce naphthyridine mono-A-oxides by reaction of the alkynyl-aldehyde with hydroxylamine instead of ammonia. 

Suitably designed naphthyridine-based ligands allowed the introduction of aryl C-H bond at axial site of the [Ru2(CO)4] unit [96]. The ligand systems that were studied are collected in Scheme 14. In noncoordinating solvent DCM, reaction of ligand with [Ru2(CO)4] core led to a series of complexes, each... 

Beside the above aryl amide macrocycles, one-pot intramolecular H-bond-directed macrocyclization reactions have also been demonstrated to work with macrocycles containing formamidine [13], urea [13, 76, 77], hydrazide [78], and Schiff-base [40, 79] linkages. Using naphthyridine-based building blocks (22a), Cuccia and coworkers synthesized macrocycles containing formamidine- (22b) and urea-linkages... 

Jung, M.E. and Dansereau, S.M.K. (1994) Benzo[H]-l,6-naphthyridine synthesis via intramolecular Diels-Alder reactions of aryl oxazoles synthetic approach to 2-bromoleptoclinidinone. Heterocycles, 39, 767-778. 

---