Condensations pyridine

In contrast to the iV-imines 11, which yield solely bicyclic 1,2-diazepines 12 on irradiation, the [c]-fused pyridine /V-imincs 13 give mixtures of condensed 1,2- and 1,3-diazepines, 14 and 15, accompanied by condensed pyridines 16 (if R3 = H).145... 

Irradiation of the Condensed Pyridine A -Ethoxycarbonylimines 13a-f General Procedure 145... 

The cobalt-catalyzed cooligomerization of diynes with nitriles allows a simple one-step synthesis222 of condensed pyridine derivatives including difficultly accessible 5,6,7,8-tetrahydroisoquinolines223 The synthesis is a versatile one in that pyridines condensed with five- and seven-membered carbocyclic rings can also be achieved in moderate yield in similar fashion. Additional attractive features of this simple synthesis are the formation of condensed isoquinolines by the use of functionalized nitriles and the pronounced regioselectivity observed when dissymmetrical diacetylenes are employed (Scheme 148).222... 

Diaz-Ortiz described the cycloaddition of 4,6-dimethyl-l,2,3-triazine (105) with en-amines to give condensed pyridine systems [82]. These reactions were performed in a monomode reactor at a power of 270 W for 20 min at 15 °C. The reactions can also be performed with pyrrolidine, with cyclic ketones used as precursors of the enam-... 

The ring closure of aminomethylenemalonates (278) in Dowtherm A at 240°C for 0.5 hr under nitrogen afforded the corresponding condensed pyridine-3-carboxylates (678, X as in 278) (86EUP168350 87USP4647566). 

The ring closure of )V-(a-N-heterocyclic)aminomethylenemalonates may lead to the formation of nitrogen bridgehead pyrimidinones when the ring nitrogen is involved in the cyclization. Ring closure may also lead to the formation of condensed pyridines when the ring carbon is involved (Scheme 46). 

The one-pot reaction of a piperidin-4-one, carbon disulfide, and 1,1-dicyanomethane generates condensed thio-pyranthiones (Scheme 46). These products are reactive to ring opening and react with amines to give condensed pyridines and ultimately [2,7]naphthyridines <1999CHE799>. 

Condensed pyridines were obtained when 1,2,4-triazines reacted with cyclic alkenes. Trichloro-l,2,4-triazine (73) afforded the condensed pyridines (370a, b) in high yield with cyclopentene and (Z)-cyclooctene, respectively. In the reaction with cyclopentene the bis adduct (371) was isolated in small amount but the bis adduct (372a) is the sole reaction product when (73) is treated with norbornene. The more reactive trifluoro-1,2,4-triazine (325) affords bis adducts (371b, c 372b) with cyclopentene and (Z)-cyclooctene as well as with norbornene (79CC658). 

Besides the trihalo compounds (73) and (325), many other 1,2,4-triazines have been found to react with cyclopentene, cyclohexene, cycloheptene and cyclooctene to give condensed pyridines (373). In most cases p-benzoquinone was added to oxidize the initially-formed dihydropyridines (374) (69TL5171). 

Other 1,2,4-triazines react with norbornene to give either the condensed pyridines (375) and/or the bis adducts (372). The ratio of the two products depends on the reaction conditions and the relative proportions of reactants (69TL5171). 

When 3-phenyl-l,2,4-triazine (411) reacts with the enamine (406), orientation B is followed. In this case the 3,4-dihydropyridine (412) is formed and is isolated. Elimination of the amine directly is unfavourable, because of the cis orientation, and transfer of the proton to the pyridine nitrogen is impossible. Oxidation to the (V-oxide (413) and Cope elimination affords the condensed pyridine (414) (78UP21900). 

Intramolecular Diels-Alder reactions of 1,2,4-triazines provide convenient access to condensed pyridine heterocycles. On this basis, thermolysis of propynylthiophenylamino-1,2,4-triazines (111) in refluxing bromo-benzene over a period of 2-5 days afforded 5,ll-dihydropyrido[3,2-c][l,5]benzothiazepines (112), but in yields that were consistently less than 5% (89JOC1456). The major reaction products were pyridobenzothia-zines 113 and benzothiopyranes 114 the formation of these products, involving a six-membered transition state, is preferred to the formation of the Diels-Alder product 112, which proceeds through an entropically less favorable seven-membered transition state (Scheme 34). 

NH2- condensed pyridines (Skraup reaction) NH2-+N2 -+H, Cl, I, CN,... C02H->Br (Hunsdiecker reaction) Br-+H (Na/Hg) etc. As a matter of fact, the whole spectrum of aromatic reactivity can be transferred to indazoles substituted at the fused benzene ring. Compare, for example, the reactions described by Suschitzky et al. (68JCS(C)1937) for 2-azidonaphthalene (432) and for 5-azidoindazole (433). Pyrolysis of these compounds in a mixture of acetic and polyphosphoric acid yields (434) and (435), respectively. 

Volume 70 of Advances in Heterocyclic Chemistry consists of three chapters together with the Subject Index for Volumes 61 through 70. The first contribution by Dr. Istvan Hermecz (Chinoin, Hungary) continues with Part II of his set of three chapters on condensed pyridines. Part I, in Volume 69, covered pyrido[l,2-ft][l,2]oxazines, -thiazines, and -pyridazines, and the present chapter deals with [l,2-c]-fused 1,3-oxanes, 1,2-thiazines, and -pyrimidines. The third part will appear in a subsequent volume of our series and will deal with 1,4-oxazines and 1,4-thiazines, fused pyridine rings. 

Over the last twenty years, the cycloaddition reactions of 1,2,4-triazines have been studied intensively. 1,2,4-Triazincs arc clcctron-dcficicnt systems and readily undergo Diels-Alder reactions with inverse electron demand with electron-rich dienophiles, such as enamines and ynamines, or with systems containing strained double bonds. Inter- and intramolecular cycloaddition reactions have been observed, giving pyridines and pyrimidines or condensed pyridines and pyrimidines. 

Thus, 3,5,6-trichloro-l,2,4-triazine affords the condensed pyridines 6 in high yield when reacted with cyclopentene (77%) or (Z)-cyclooctene (80%), respectively387 (see Houben-Weyl, Vol. E7b, p 476 ff). In the reaction with cyclopentene the bisadduct 7 is isolated in small amounts. The bisadduct is the sole product when the trichloro compound is reacted with bicyclo[2.2.1]hept-2-ene. The more reactive 3,5,6-trifluoro-l,2,4-triazine affords the bisadducts with cyclopentene and (Z)-cyclooctenc as well as with bicyclo[2.2.1]hept-2-ene, e.g. formation of 8 (X = F).385... 

In addition to the trihalo compounds, many other 1,2,4-triazines have been found to react with cyclopentene, cyclohexene, cycloheptene and cyclooctene to give condensed pyridines. In most cases, 1,4-benzoquinone is added to oxidize the initially formed dihydropyridines and to prevent a second [4 I 2] cycloaddition.386 Other 1,2,4-triazines also react with bicyclo[2.2.1]hept-2-ene to give either the condensed pyridines and/or the bisadducts. The ratio of the two products depends on the reaction conditions and the relative proportions of the reactants.386 For a detailed survey, see Houben-Weyl, Vol. E7b, p471ff. 

Methyl groups vicinal to cyano substituents in azines readily condense with dimethylformamide dimethylacetal (DMFDMA) to yield dimethyl-aminoethenyl intermediates, which cyclize to give condensed pyridines in both acid and alkaline media. For example, reaction of the cyanopicolines (18, 19) with DMFDMA gives the enamines (20, 21), which are readily converted into the pyridopyridines (22, 23) on heating with HBr-AcOH (78JOC4878), Scheme 6. 

Intramolecular Diels-Alder reactions have also found wide application in the chemistry of 3-substituted-l,2,4-triazines, bearing an appropriate dienophilic fragment at C-3, as efficient synthetic routes to condensed pyridines (Scheme 102) <2000T1165, 2000T8489, 2003TL4495, 2004JOC7171>. 

There are numerous examples of construction of condensed pyridines (and also quinolines and acridines) via cascade reactions, involving conversion of the adducts of benzylic or allylic carbanions to nitroarenes followed by their intramolecular cyclization to form the pyridine ring. Thus, the reaction between 4-chloronitrobenzene and phenylacetonitrile, which is known to produce in protic media the corresponding 2,1-benzisoxazole via conversion of the intermediate adduct into nitrosoarene and its further condensation reaction [80], can proceed in aprotic media along another way. The same o adduct formed in tetrahydrofuran, when treated with trialkylchlorosilanes or pivaloyl chloride, undergoes cycUzatiOTi into acridine derivative (Scheme 85) [208]. 

During the stabilization process, dehydrogenation, oxidation, and nitrile cy-clization reactions result in the formation of a condensed pyridine ring ladder structure that is suitable for subsequent carbonization (29). The general mechanism is shown in Figure 7. The details of the stabilization mechanism are highly... 

A new thiophene-based monomer bearing a condensed pyridine group (84) was synthesized to obtain a low-gap polymer but the maximum absorption of the polymer was found at a high energy (560 nm, 2.2 eV) [336]. A real lowering of the gap was obtained from a condensed thiadiazole unit (85) with maximum polymer absorption at 934 nm (1.3 eV) [337]. Recently by further insertion of a pyrazine ring (86) the maximum absorption has been increased to 990 nm (1.25 eV) and the threshold of absorption lowered to 0.3 eV [338] so... 

Condensed pyridine ring from o-aminooxo compounds Friedlander synthesis... 

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