One-pot synthesis, of pyridines

Examples of nitrogen-containing heterocycle syntheses based on condensation reactions continue to be forthcoming. Examples include a tandem oxidation-annulation of propargyl alcohols in a one-pot synthesis of pyridines (Equation 148) <2003SL1443>, trifluoromethyl-substituted pyridines (Scheme 94) <2003S1531>, and standard malononitrile additions to a,/3-unsaturated ketones <1995JCM392>. 

MUller reports a four component, one-pot synthesis of pyridines <02TL6907>. For example, aryl halide 15 and propargylic alcohol 16 were combined in the presence of copper and palladium to afford enone 17. The addition of cyclic enamine 18 led to Michael addition and the subsequent cyclocondensation was achieved by adding ammonium chloride and acetic acid (19—>20). Other multicomponent approaches to substituted pyridines have been reports by Litvinov <02RCBIE362>, Elkholy <02SC3493> and Veronese <02T9709>. 

Bagley MC, Hughes DD, Sabo HM, Taylor PH, Xiong X (2003) One-pot synthesis of pyridines or pyrimidines by tandem oxidation-heteroannulation of propargylic alcohols. 

Stanforth and co-workers made additional improvements on the hetero-Diels-Alder approach. They accomplished a one-pot synthesis of pyridines from a p-diketoesters and amidrazones <04T8893>. Deniaud et al. has investigated diazadienium iodide 15 as an aza-diene moiety in the synthesis of pyridines <04TL9557>. They have demonstrated that diazadienium iodide 15 reacts with ketenes, acetylenes and acrylic dienophiles to yield a variety of substituted pyridines as shown in Scheme 5. 

Rhodium-catalyzed chelation-assisted C—H bond functionalization reactions (enantioselective annulation of aryl imines, dihydropyridine synthesis from imines and ahcynes, one-pot synthesis of pyridines from imines and alkynes, 2-arylpyridine alkylation with imines) 12ACR814. Synthesis of pyridine and dihydropyridine derivatives by regjo- and stereoselective addition to N-activated pyridines 12CRV2642. 

Bondock, S., 2005. One-pot synthesis of pyridine derivatives via Diels-Alder reactions of 2,4-dimethyl-5-methoxyoxazole. Heteroatom Chemistry. 16 49-55. 

A rapid one-pot synthesis of imidazo-[l,2-a]-pyridines, pyrazines and pyrimidines was described in 1999 by Varma et al. [50], who used recyclable montmorillonite clay Kio under solvent-free conditions and microwave irradiation (Scheme 8.32). 

The one-pot synthesis of 4-azaindole is also initiated by photoirradiation 3-amino-2-chloro-pyridine and acetaldehyde are the starting materials (Fontan et al. 1981 Scheme 7.37). 

More recently, Shen et al. reported on a green and efficient three-component one-pot synthesis of 2-aryl-pyridines with the same starting materials as the Hanztsch reaction, under solvent-, catalyst-, and heat-free conditions. This methodology does... 

Kantevari S, Chary MV, Vuppalapati SVN (2007) A highly efficient regioselective one-pot synthesis of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones using K5CoW12O40 center dot 3H(2)0 as a heterogeneous recyclable catalyst. Tetrahedron 63 13024-13031... 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

There are relatively few synthetic routes to 2,7-naphthyridines almost all are multistage and rely on annulation of a second pyridine ring to a suitably functionalised pyridine precursor. French workers have described an efficient, one-pot synthesis of l,3,6,8-tetramethyl-2,7-naphthyridine 1 which involves treatment of a mixture of acetyl chloride (1.6 mol) and aluminium chloride (0.3 mol) with t-butanol or t-butyl chloride (0.1 mol) at 35°C for half an hour, followed by careful addition of the reaction mixture to liquid ammonia. This gave 37% of 2,4,6-trimethylpyridine and 63% of the naphthyridine 1 in a total yield of 91%. 

Tu S, Zhou D, Cao L et al (2009) A simple three-component condensation highly efficient microwave-assisted one-pot synthesis of polyfunctional pyridine derivatives. J Heterocycl Chem 46 54-57... 

A convenient one-pot synthesis of benzisothiazolones 344 (R = H, R = NH2, R = H) has been developed using a cyclization reaction in which the acyl azide 398 (X = CH) was used as an intermediate. Similarly, 2-mercaptonicotinic acyl azide 398 (X = N) affords the corresponding isothiazolo[5,4-/)]pyridin-3(2//)-one <2000SL1427>. 

During the large-scale, high-yield, one-pot synthesis of 4-chloro-3-(hydroxymethyl)pyridine, a starting material for the preparation of several polyfunctionalized molecules that can be linked to cephalosporines, M. Penso and co-workers utilized the combination of direct regioseiective iithiation/formyiation and crossed-Cannizzaro reduction of 4-chloropyridine. ... 

A regioselective one-pot synthesis of 2-substituted pyridines from pyridine N-oxides has been described. The pyridine N-oxide 89 in tetrahydrofuran... 

Shaabani A, Soleimani E, Maleki A (2006) Ionic liquid promoted one-pot synthesis of 3- aminoimidazo[l,2-a]pyridines. Tetrahedron Lett 47 3031-3034... 

Recently, Ranu and coworkers [45] used basic ionic liquid, l-butyl-3-methyUm-idazolium hydroxide [bmimJOH, in place of conventional bases to provide a selective, high-yielding one-pot synthesis of highly substituted pyridines through a three-component condensation of aldehydes, malononitrile, and Ihiophenols at room temperature (Scheme 17.3). The other advantages of this procedure are a lack of hazardous organic solvents in the reaction and the reusability of ionic liquids. 

Scheme 17.3 A one-pot synthesis of highly substituted pyridines under [bmimJOH ionic liquid...

A facile one-pot synthesis of trifluoromethyl-substituted pyridine derivatives has been reported (93JHC71). The procedure depends on the high reactivity of trifluroacetoacetyl chloride, which is generated in situ from trifluoroacetyl chloride and ketene. Thus, the enaminone 391 gives the intermediate enamide 392, which is refluxed in triethylamine to give the... 

A rapid one-pot synthesis of imidazo[l,2-a]pyridines, pyrazines and pyrimidines was described in 1999 by Varma and Kumar, who used recyclable montmorillonite clay Kio under solvent-free conditions with microwave irradiation (Scheme 10.114) [223]. The whole process, formation of the iminium ion by condensation of the aldehyde with an amine (1 min at 900 W in a domestic oven) then nucleophilic attack of the isocyanide (1 min at 450 W and 1 min cooling) took 3 min and gave the pure products in yields ranging from 56 to 88%. 

Aryloxazole-4-aldehydes 59 (R = H, Me, Cl, Br or Ph) are formed in good yields in the reaction of 2-azidoacetophenones 58 with the Vilsmeier reagent dimethylformamide-phosphorus oxychloride <97TL6089>. A one-pot synthesis of the cyanooxazoleamines 60 is by the action of dicyclohexylcarbodiimide and pyridine on mixtures of aminonalononitrile tosylate and carboxylic acids <97S861>. 

The direct one-pot synthesis of 2,5-di(4-pyridyl)thiophene has been achieved by the palladium catalyzed cross-coupling between 4-(trimethylstannyl)pyridine and 2,5-dibromothiophene <92BCJ1855,92CC620). These are useful precursors for viologens with potential application as molecular electronic devices. 

Cheng and co-workers reported a one-pot synthesis of substituted pyridines through a rhodium-catalyzed C-H alkenylation of a,(3-unsaturated ketoximes 287 with symmetrical alkyne substrates 288. 67t-Electro-cyclization of the azatriene intermediates 289 and subsequent loss of water afforded the desired pyridines 290 in moderate to good yields. ... 

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